For  Reference 


NOT  TO  BE  TAKEN  FROM  THIS  ROOM 


Frontispiece. 


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Solar  spectrum  with  Fraunhofer  lines.    2.  Absorption  spectrum  of  a  concentrated  solution  of  oxyhse 

globin;  all  the  light  is  absorbed  except  in  the  red  and  orange.    "•.  Absorption  spectrum  of  a  les>  concentri 

solution  of  oxyhemoglobin,     i.  Absorption  spectrum  of  a  dilute  solution  of  oxyhemoglobin,  showing  tin 

characteristic  bands.    •">.  Absorption  spectrum  of  a  very  dilute  solution  of  oxyhsemoglobin,  showing  only 

6    Absorption  spectrum  of  a  dilute  solution  of  reduced  haemoglobin,  showing  the  characteristic  .-' 

ed  with  spectrum  4).    7.  Absorption  Bpectrum  of  a  dilute  solution  of  carbon-monoi 

haemoglobin  (to  be  compared  with  spectrum  I).     8.  Absorption  spectrum  of  metheemoglobin.    9.  Absoi  H 

spectrum  of  acid  h  tlcoholic  solution).    10.  Absorption  spectrum  of  alkaline  haematin  (alcoholic  - 

odifled  from  MacMunn,  Thi  Specb-oscopt  in  Medicine). 


AN  AMERICAN  TEXT-BOOK 


OF 


PHYSIOLOGY 

LM  Angeles,  CaJ, 
HENRY  P.  BOWDITCH,  M.  D.  WARREN   P.  LOMBARD,  M.  D. 

JOHN  G.  CURTIS,  M.D.  GRAHAM  LUSK,  Ph.D.,  F.R.S.  (EDIN.) 

HENRY  H.  DONALDSON,  Ph.  D.  W.  T.  PORTER,  M.D. 

W.  H.  HOWELL,  Ph.D.,  M.D.  EDWARD  T.  REICHERT,  M.D. 

FREDERIC  S.  LEE,  Ph.D.  HENRY  SEW  ALL,  Ph.D.,  M.D. 


EDITED   BY 

WILLIAM  H.  HOWELL,  Ph.D.,  M.D. 

Professor  of  Physiology  in  the  Johns  Hopkins  University,  Baltimore,  Md. 


SECOND  EDITION,  REVISED 


Vol.  I. 

BLOOD,  LYMPH,  AND   CIRCULATION;  SECRETION,  DIGESTION 

AND  NUTRITION;  RESPIRATION  AND  ANIMAL  HEAT; 

CHEMISTRY   OF   THE   BODY 


PHILADELPHIA  AND  LONDON 

W.  B.  SAUNDERS    &    COMPANY 

1901 


I  4 


Copyright,  1900. 
By  W.  B.  SAUNDERS    &   COMPANY. 


ELECTROTYPED  BY  PRESS  OF 

WESTCOTT   *  THOMSON      PHILAOA.  W-    B-    SAUNDERS  &   COMPA 


CONTRIBUTORS  TO  VOL.  L 


JOHN  G.  CURTIS,  M.D., 

Professor  of  Physiology  in  Columbia  University  (College  of  Physicians  and  Surgeons). 

W.  H.  HOWELL,  Ph.  D.,  M.  D., 

Professor  of  Physiology  in  the  Johns  Hopkins  University. 

GRAHAM   LUSK,  Ph.D.,  F.  R.  S.  (Edin.), 

Professor  of  Physiology  in  the  University  and  Belle vue  Hospital  Medical  College,  New 
York. 

W.  T.  PORTER,  M.D., 

Associate  Professor  of  Physiology  in  the  Harvard  Medical  School. 

EDWARD  T.  REICHERT,  M.  D., 

Professor  of  Physiology  in  the  University  of  Pennsylvania. 


PREFACE  TO  THE  SECOND  EDITION. 


Advantage  has  been  taken  of  the  necessity  of  issuing  a  second  edition 
of  the  American  Text-Book  of  Physiology  to  alter  somewhat  its  general 
arrangement.  The  book  has  proved  to  be  successful,  and  for  the  most  part 
has  met  only  with  kindly  and  encouraging  criticisms  from  those  who  have 
made  use  of  it.  Many  teachers,  however,  have  suggested  that  the  size  of 
the  book,  when  issued  in  a  single  volume,  has  constituted  to  some  extent  an 
inconvenience  when  regarded  from  the  standpoint  of  a  student's  text- book 
that  may  be  needed  daily  for  consultation  in  the  lecture-room  or  the  labora- 
tory. It  has  been  thought  best,  therefore,  to  issue  the  present  edition  in  two 
volumes,  with  the  hope  that  the  book  may  thereby  be  made  more  serviceable 
to  those  for  whose  aid  it  was  especially  written. 

This  change  in  the  appearance  of  the  book  has  necessitated  also  some 
alteration  in  the  arrangement  of  the  sections,  the  part  upon  the  Physiology 
of  Nerve  and  Muscle  being  transferred  to  the  second  volume,  so  as  to  bring  it 
into  its  natural  relations  with  the  Physiology  of  the  Central  Nervous  System. 

The  actual  amount  of  material  in  the  book  remains  substantially  the  same 
as  in  the  first  edition,  although,  naturally,  very  many  changes  have  been 
made.  Even  in  the  short  time  that  has  elapsed  since  the  appearance  of  the 
first  edition  there  has  been  much  progress  in  physiology,  as  the  result  of  the 
constant  activity  of  experimenters  in  this  and  the  related  sciences  in  all  parts 
of  the  world,  and  an  effort  has  been  made  by  the  various  contributors  to  keep 
pace  with  this  progress.  Statements  and  theories  that  have  been  shown  to 
be  wrong  or  improbable  have  been  eliminated,  and  the  new  facts  discovered 
and  the  newer  points  of  view  have  been  incorporated  so  far  as  possible.  Such 
changes  are  found  scattered  throughout  the  book. 

The  only  distinctly  new  matter  that  can  be  referred  to  specifically  is  found 
in  the  section  upon  the  Central  Nervous  System,  and  in  a  short  section  upon  the 
modern  ideas  and  nomenclature  of  physical  chemistry,  with  reference  especially 
to  the  processes  of  osmosis  and  diffusion.  The  section  dealing  with  the  <  Vntral 
Nervous  System  has  been  recast  in  large  part,  with  the  intention  of  making 
it  more  suitable  to  the  actual  needs  of  medical  students  ;  while  a  brief  presen- 
tation of  some  of  the  elementary  conceptions  of  physical  chemistry  seems  to 
he  necessary  at  the  present  time,  owing  to  the  large  part  that  these  views  are 
taking  in  current  discussions  in  physiological  and  medical  literature. 

The  index  has  been  revised  thoroughly  and  considerably  amplified,  a  table 
of  contents  has  been  added  to  each  volume,  and  numerous  new  figures  have 
been  introduced. 

August.  1900. 


PREFACE. 


The  collaboration  of  several  teachers  in  the  preparation  of  an  elementary 
text-book  of  physiology  is  unusual,  the  almost  invariable  rule  heretofore 
having  been  for  a  single  author  to  write  the  entire  book.  It  does  not  seem 
desirable  to  attempt  a  discussion  of  the  relative  merits  and  demerits  of  the  two 
plans,  since  the  method  of  collaboration  is  untried  in  the  teaching  of  physi- 
ology, and  there  is  therefore  no  basis  for  a  satisfactory  comparison.  It  is  a  fact, 
however,  that  many  teachers  of  physiology  in  this  country  have  not  been 
altogether  satisfied  with  the  text-books  at  their  disposal.  Some  of  the  more 
successful  older  books  have  not  kept  pace  with  the  rapid  changes  in  modern 
physiology,  while  few,  if  any,  of  the  newer  books  have  been  uniformly  satis- 
factory in  their  treatment  of  all  parts  of  this  many-sided  science.  Indeed,  the 
literature  of  experimental  physiology  is  so  great  that  it  would  seem  to  be 
almost  impossible  for  any  one  teacher  to  keep  thoroughly  informed  on  all 
topics.  This  fact  undoubtedly  accounts  for  some  of  the  defects  of  our  present 
text-books,  and  it  is  hoped  that  one  of  the  advantages  derived  from  the  col- 
laboration method  is  that,  owing  to  the  less  voluminous  literature  to  be 
consulted,  each  author  has  been  enabled  to  base  his  elementary  account  upon 
a  comprehensive  knowledge  of  the  part  of  the  subject  assigned  to  him.  Those 
who  are  acquainted  with  the  difficulty  of  making  a  satisfactory  elementary 
presentation  of  the  complex  and  oftentimes  unsettled  questions  of  physiology 
must  agree  that  authoritative  statements  and  generalizations,  such  as  are  fre- 
quently necessary  in  text-books  if  they  are  to  leave  any  impression  at  all  upon 
the  student,  are  usually  trustworthy  in  proportion  to  the  fulness  of  informa- 
tion possessed  by  the  writer. 

Perhaps  the  most  important  advantage  which  may  be  expected  to  follow 
the  use  of  the  collaboration  method  is  that  the  student  gains  thereby  the  point 
of  view  of  a  number  of  teachers.  In  a  measure  he  reaps  the  same  benefit  as 
would  be  obtained  by  following  courses  of  instruction  under  different  teachers. 
The  different  standpoints  assumed,  and  the  differences  in  emphasis  laid  upon 
the  various  lines  of  procedure,  chemical,  physical,  and  anatomical,  should 
give  the  student  a  better  insight  into  the  methods  of  the  science  as  it  exists 


PREFACE. 

to-day.  A  similar  advantage  may  be  expected  to  follow  the  inevitable  over- 
lapping of  the  topics  assigned  to  the  various  contributors,  since  this  has  led 
in  many  cases  to  a  treatment  of  the  same  subject  by  several  writers,  who  have 
approached  the  matter  under  discussion  from  slightly  varying  standpoints,  and 
in  a  few  instances  have  arrived  at  slightly  different  conclusions.  In  this 
last  respect  the  book  reflects  more  faithfully  perhaps  than  if  written  by  a 
single  author  the  legitimate  differences  of  opinion  which  are  held  by  physi- 
ologists at  present  with  regard  to  certain  questions,  and  in  so  far  it  fulfils 
more  perfectly  its  object  of  presenting  in  an  unprejudiced  way  the  existing 
state  of  our  knowledge.  It  is  hoped,  therefore,  that  the  diversity  in  method 
of  treatment,  which  at  first  sight  might  seem  to  be  disadvantageous,  will  prove 
to  be  the  most  attractive  feature  of  the  book. 

In  the  preparation  of  the  book  it  has  been  assumed  that  the  student  has 
previously  obtained  some  knowledge  of  gross  and  microscopic  anatomy,  or  is 
taking  courses  in  these  subjects  concurrently  with  his  physiology.  For  this 
reason  no  systematic  attempt  has  been  made  to  present  details  of  histology  or 
anatomy,  but  each  author  has  been  left  free  to  avail  himself  of  material  of 
this  kind  according  as  he  felt  the  necessity  for  it  in  developing  the  physiolog- 
ical side. 

In  response  to  a  general  desire  on  the  part  of  the  contributors,  references 
to  literature  have  been  given  in  the  book.  Some  of  the  authors  have  used 
these  freely,  even  to  the  point  of  giving  a  fairly  complete  bibliography  of  the 
subject,  while  others  have  preferred  to  employ  them  only  occasionally,  where 
the  facts  cited  are  recent  or  are  noteworthy  because  of  their  importance  or 
historical  interest.  References  of  this  character  are  not  usually  found  in  ele- 
mentary text  books,  so  that  a  brief  word  of  explanation  seems  desirable.  It 
has  not  been  supposed  that  the  student  will  necessarily  look  up  the  references 
or  commit  to  memory  the  names  of  the  authorities  quoted,  although  it  is  pos- 
sible, of  course,  that  individual  students  may  be  led  to  refer  occasionally  to 
original  sources,  and  thereby  acquire  a  truer  knowledge  of  the  subject.  The 
main  result  hoped  for,  however,  is  a  healthful  pedagogical  influence.  It  is  too 
often  the  case  that  the  student  of  medicine,  or  indeed  the  graduate  in  medicine, 
regards  his  text-book  as  a  final  authority,  losing  sight  of  the  fad  that  such 
books  are  mainly  compilations  from  the  works  of  various  investigators,  and 
that  in  all  matters  in  dispute  in  physiology  the  final  decision  must  be  made,  so 
far  as  possible,  upon  the  evidence  furnished  by  experimental  work.  To  enforce 
this  latter  idea  and  to  indicate  the  character  and  source  of  the  great  literature 
from  which  the  material  of  the  text-book  is  obtained  have  been  the  main 
reasons  for  the  adoption  of  the  reference  system.     It  is  hoped  also  that  the 


PREFACE. 

book  will  be  found  useful  to  many  practitioners  of  medicine  who  may  wish  to 
keep  themselves  in  touch  with  the  development  of  modern  physiology.  For  this 
class  "I  readers  references  to  literature  are  not  only  valuable,  but  frequently 
essential,  since  the  limits  of  a  text-book  forbid  an  exhaustive  discussion  of 
mauv  points  of  interesl  concerning  which  fuller  information  may  be  desired. 

The  numerous  additions  which  are  constantly  being  made  to  the  literature 
of  physiology  and  the  closely  related  sciences  make  it  a  matter  of  difficulty  to 
escape  errors  of  statement  in  any  elementary  treatment  of  the  subject.  It  can- 
not be  hoped  that  this  book  will  be  found  entirely  free  from  defects  of  this 
character,  but  an  earnest  effort  has  been  made  to  render  it  a  reliable  repository 
of  the  important  facts  and  principles  of  physiology,  and,  moreover,  to  embody 
in  it,  so  far  as  possible,  the  recent  discoveries  and  tendencies  which  have  so 
characterized  the  history  of  this  science  within  the  last  few  years. 


CONTENTS  OF  VOLUME  I. 


INTRODUCTION  (By  W.  H.  Howell) 17 

Definition  of  physiology  and  protoplasm,  17 — Animal  and  plant  physiology,  17 — Vital 
irritability,  18 — Nutrition,  assimilation  and  disassimilation,  auabolism,  kataholism, 
metabolism,  19 — Reproduction,  20,28 — Contractility  and  conductivity,  20 — Physiologi- 
cal division  of  labor,  22 — Pfliiger  hypothesis  of  the  structure  of  the  living  molecule, 
23 — Loew's  and  Latham's  hypothesis  of  the  structure  of  the  living  molecule,  23 — The 
chemical  structure  of  proteids,  protamine,  24 — Physical  structure  of  living  matter,  24 
— Vital  force,  25 — Secretion  and  absorption,  27 — Heredity  and  consciousness,  28 — Gen- 
eral and  special  physiology,  29 — Methods  of  investigation  used  in  the  science  of 
physiology,  30. 

BLOOD  (By  W.  H.  Howell) 33 

A.  General  Properties — Physiology  of  the  Corpuscles 33 

Histological  structure  of  blood,  33 — Definition  of  blood-plasma,  blood-serum,  and 
defibrinated  blood,  33 — Reaction  of  blood,  34— Specific  gravity  of  blood,  34 — Histology 
of  red  corpuscles,  35 — Condition  of  the  haemoglobin  in  the  red  corpuscles,  35 — Laking 
of  blood,  35 — Globulicidal  and  toxic  action  of  blood-serum,  36 — Isotonic,  hypertonic, 
hypotonic  solutions,  36 — Nature  and  amount  of  hfemoglobin,  37 — Compounds  of  haemo- 
globin with  O,  CO,  NO.  and  CO2,  38— The  iron  of  the  haemoglobin  molecule,  39— Haemo- 
globin crystals,  40 — Absorption  spectra  of  haemoglobin,  40 — Derivative  compounds  of 
haemoglobin,  44— Origin  and  fate  of  the  red  corpuscles,  45 — Variations  in  the  number 
of  red  corpuscles,  46 — Morphology  and  physiology  of  the  leucocytes,  47 — Physiology 
of  the  blood  plates,  49. 

B     Chemical   Composition   op   the   Blood — Coagulation — Total   Quantity  of 

Blood — Regeneration  after  Hemorrhage 50 

Composition  of  the  plasma  and  corpuscles,  50 — Proteids  of  the  blood  plasma,  51 — 
Serum  albumin,  52 — Paraglobulin,  53 — Fibrinogen,  53 — Coagulation  of  blood,  super- 
ficial appearances,  54 — Time  of  clottiug,  55 — Theories  of  coagulation,  55 — Nature  and 
origin  of  fibrin  ferment,  58 — Intravascular  clotting,  60 — Means  of  hastening  or  retard- 
ing clotting,  61 — Total  quantity  of  blood  in  the  body,  63 — Regeneration  of  the  blood 
after  hemorrhage,  63 — Transfusion  of  blood  and  salines,  64. 

C.     Diffusion  and  Osmosis,  and  Their  Importance  in  the  Body      65 

Osmotic  pressure,  65 — Calculation  of,  67 — Electrolysis,  67 — Grammolecular  solutions, 
67 — Osmotic  pressure  of  proteids,  69 — Diffusion  of  proteids,  70. 

LYMPH  (By  W.  H.  Howell) 70 

Lymph-vascular  system,  70 — Formation  of  lymph,  theories  of,  70 — The  factors  con- 
trolling the  flow  of  lymph,  75,  145 — Pressure  in  lymph-vessels,  146 — Effect  of  thoracic 
aspiration  on  lymph-flow,  147— Effect  of  body  movements  and  valves  on  lymph-flow, 
147. 

CIRCULATION 70 

PART  I. — The  Mechanics  of  the  Circulation  of  the  Blood  and  of  the  Move- 
ment of  the  Lymph     (By  John  G.  Curtis) 76 

A.  General  Considerations      76 

General  course  of  the  blood-flow,  76 — Causes  of  the  blood-flow,  77 — Working  of  die 
pumping  mechanism,  78 — Pulmonary  circuit,  78. 

B.  Movement  of  the  Blood  in  the  Capillaries,  Arteries,   \m>  Veins    ....     79 

Anatomical  characteristics  of  the  capillaries,  79— The  circulation  as  observed  under 
the  microscope,  80 — Behavior  of  the  red  corpuscles,  81  Friction,  axial  stream,  and 
inert   layer,  81 — Behavior  of  the  leucocyte-,  82     Emigration  of  the  leucocytes,  83 

Velocity  of  the  blood  in  the  small  vessels,  S3     Capillary  blood-pressure.  84 

C.  The  Pressure  of  the  Blood  in  the  Arteries,  Capillaries,  lnd  Veins  ...    85 

Method  of  studying  bl 1-pressure,  manometers,  85— The  mercurial  manometer  and 

graphic  record  of  blood-pressure  upon  a  kymograph,  88 — The  mean  pressure  in  arteries 
and  veins,  90. 

9 


10  CONTENTS. 

PAGE 

D.  The  Causes  of  the  Pressure  in  the  Arteries,  Capillaries,  and  Veins   ...     91 
Balance  of  the  factors  producing  arterial  pressure,  92 — The  arterial  pulse,  93 — The 

capillary  pressure  and  its  cause,  93-  Extinction  of  tile  arterial  pulse  in  the  capillaries, 
94 — Venous  pressure  and  its  causes,  94—  Subsidiary  forces  assisting  the  blood-flow,  95 — 
Respiratory  pulse  in  the  veins,  96 — The  dangerous  region,  entrance  of  air  into  veins,  97. 

E.  The  Velocity  of  the  Blood  in  Arteries,  Capillaries,  and  Veins 98 

Measurement    of  velocity   in   large  vessels.   Stromuhr,   98 — Measurement  of  rapid 

changes  in  velocity,  Kin — Velocity  and  pressure  of  blood  compared,  KM  —  Relation  of 
velocity  to  the  sectional  area  of  the  vascular  bed,  102 — Time  spent  by  blood  in 
capillary,  103. 

F.  The  Blood-flow  through  the  Linus 103 

(}.    The  Pulse  Volume  and  the  Work  Done  by  the  Ventricles 104 

The    cardiac  cycle,  104 — The  pulse  volume,  105 — The  work  of   the   ventricles,  106 — 
Heart's  contraction  as  a  source  of  heat,  108. 
II.    The  Mechanism  of  the  Valves  of  the  Heart 108 

I'se  of  the   valves.  108 — The  auriculoventricular  valves,  108 — Use  of  the   tendinous 
cords,  109 — The  papillary  muscles   and    their    uses,  110 — The   semilunar  valves,  110 — 
Lunuhe  and  corpora  arantii,  111. 
I.    The  Changes  in  Form  and  Position  of  the  Beating  Heart,  and  the  Cardiac 

Impulse 112 

General  changes  in  the  heart  and  arteries,  112 — The  heart  and  vessels  in  the  open 
chest,  113 — Changes  of  size  and  form  in  the  beating  ventricles,  113 — Changes  of  posi- 
tion of  the  ventricle,  114 — Changes  in  the  auricle,  great  veins,  and  great  arteries,  115 
—  Effects  of  opening  the  chest,  115 — Probable  changes  in  heart  in  the  unopened  chest, 
116 — The  cardiac  impulse   or  apex  beat,  117. 

J.    The  Sounds  of  the  Heart 118 

Relations  and  character  of  the  heart-sounds,  118 — Cause  of  the  second  sound,  118 — 
Causes  of  the  first  sound,  119. 

K.    The  Frequency  of  the  Cardiac  Cycles 121 

L.    The  Relations  in  Time  of  the  Main  Events  of  the  Cardiac  Cycle  ....  121 
The  auricular,    ventricular,   and   cardiac  cycles,  122 — The  variability  of  each  cycle, 
123 — Relative    lengths  of  ventricular  systole  and  diastole,  123 — Lengths  of  auricular 
systole  and  heart  pause,  124. 

M.    The  Pressure  Within  the  Ventricles 125 

Range  of  pressure  within  ventricles,  125 — Methods  of  recording  ventricular  press- 
ures. 126 — General  character  of  curve  of  intraventricular  pressure,  128 — Effect  of 
auricular  systole  on  the  curve  of  ventricular  pressure.  130— The  opening  and  closing 
of  the  heart  valves  in  relation  to  the  curve  of  ventricular  pressure,  130— Analysis  of 
the  curve  of  ventricular  pressure,  133 — Negative  pressure  within  the  ventricles,  134. 

N.    The  Functions  of  the  Auricles 135 

The  auricle  as  a  force  pump.  135 — Time  relations  of  auricular  systole  and  diastole, 
136 — Statement  of  functions  of  auricles,  l.;i;  Negative  pressure  within  the  auricles, 
137— Is  the  auricle  emptied  by  its  systole?  138— Question  of  regurgitation  from  auri- 
cles to  veins,  138. 

O.    The  Arterial  Pulse       139 

Nature  and  importance  of  the  arterial  pulse,  139— Rate  of  transmission  of  the  pulse- 
wave,  1  1(1  Frequency  and  regularity  of  the  pulse,  141  — Arterial  tension  as  indicated 
by  the  pulse,  141— Size  and  celerity  of  pulse.  1  II  The  pulse-trace,  or  sphygmogram. 
142— Analysis  of  the  sphygmogram,  143— The  dicrotic  wave,  143— The  diagnostic  use 
of  i  lie  sphygmogram.  115. 

Part  II.— The  [nnervation  ok  the  Heart  (By  W.  T.  Porter) 148 

The  cause  of  the  rhythmic  heart-heat.  IIS  The  intracardiac  ganglion  ells  and 
nerves,  148— The  nerve  theory  of  the  heart-beat,  149— The  muscular  theory  of  the 
heart-beat,  150  The  excitation  wave  and  its  passage  over  the  heart,  152  The  passage 
of  the  excitation  wave  from  auricle  to  ventricle,  154— The  refractory  period  and  com- 
pensatory pause,  156, 
A.    The  Cardiac  Nerves     159 

Anatomical  arrangement  of  the  heart  nerves,  159  The  inhibitory  nerves.  161  — 
Effect  of  inhibition  on  the  ventricles  162— Effect  of  inhibition  on  the  auricle  and 
sinus,  L64  Effect  of  inhibition  on  the  bulbus  arteriosus,  165  Effect  of  inhibition  on 
the  irritability  of  the  heart.  165  Relation  of  inhibition  to  rate  and  strength  of  stim- 
ulus, 165  -Arrest  of  the  heart  in  systole,  165— Comparative  inhibitory  power  of  the 
two  vagi.  166  Effect  of  the  septal  nerves  on  the  inhibition,  166— Theories  of  the 
nature  of  vagus  inhibition,  L66  Relation  of  age,  temperature,  and  intracardiac  press- 
are  to  inhibition,  167 — The  augmentor  or  accelerator  nerves  of  the  heart,  167 — Effect 
of  stimulating  the  augmentor  nerves,  Kill  Simultaneous  stimulation  of  the  accelerator 
and  inhibitory  fibres,  17<»  classification  of  the  inhibitory  and  augmentor  fibres,  171 — 
The  centripetal    nerves  of  the  heart.  172      Existence  of  sensory  nerves  in   the  heart, 


CONTENTS.  11 

FAGE 

172 — The  depressor  nerve  of  the  heart,  172 — Analysis  of  the  effect  of  stimulation  of 
the  depressor  nerve,  173 — Keflex  etTeet  of  sensory  nerves  on  the  heart,  175 — Reflex 
effects  through  the  sympathetic  system  on  the  heart,  175. 

B.  The  Centres  of  the  Heart-nerves 170 

The  inhibitory  centre,  176 — Tonus  of  the  inhibitory  centre,  176 — Origin  of  the  car- 

dio-inhibitory  fibres,  177 — Position  of  the  augmentor  centre,  177 — Action  of  higher 
parts  of  the  brain  on  the  cardiac  centres,  178— The  existence  of  peripheral  reflex 
centres,  178 — Ligatures  of  Stan n ins,  17."v 

Part  III.— The  Nutrition  of  the  Heart  (By  W.  T.  Porter) 179 

Spongy  structure  of  frog's  heart,  179—  The  coronary  arteries  iu  the  dog,  179 — The 
terminal  nature  of  coronary  arteries,  180— The  effect  of  closure  of  the  coronary  arte- 
ries, 181 — The  cause  of  the  arrest  of  the  heart  after  closure  of  the  coronary  arteries, 
182— Fibrillary  contractions  and  recovery  from,  183— Closure  of  the  coronary  veins, 
184 — The  volume  of  the  coronary  circulation,  184—  The  effect  of  the  heart-eontractious 
on  the  coronary  circulation,  185 — The  vessels  of  Thebesius  and  the  coronary  veins, 
186— Blood-supply  and  heart-beat,  186— Lymphatics  of  the  heart,  186. 

C.  Solutions  which  Maintain  the  Beat  of  the  Heart 187 

Methods  of  nourishing  the  heart  with  solutions,  187 — The  composition  and  action  of 

nutrient  solutions,  189— The  effect  of  CO2,  organic  substances,  and  physical  character- 
istics of  nutrient  solutions,  191— Nourishment  of  the  isolated  mammalian  heart,  191. 

Part  IV.— The  Innervation  of  the  Blood-vessels  (By  W.  T.  Porter) 192 

Historical  account  of  the  discovery  of  vaso-motor  nerves,  192— Methods  of  demon- 
strating vaso-motor  phenomena,  195— Experimental  distinctions  between  vaso-const  ric- 
tor  and  vaso-dilator  nerve-fibres,  196 — Anatomical  course  of  vaso-motor  fibres.  197— 
Vaso-motor  centre  in  the  medulla,  198— Vaso-motor  centres  in  the  spinal  cord,  199— 
Sympathetic  vaso-motor  centres— peripheral  tone,  200— Rhythmical  changes  in  vascular 
tone,  201 — Vaso-motor  reflexes,  201,  202— Relation  of  cerebrum  to  vaso-motor  centres, 
202 — Pressor  and  depressor  fibres,  202— Vaso-motor  fibres  to  the  brain,  203— Vaso-motor 
fibres  to  the  head,  204— Vaso-motor  fibres  to  the  lungs,  21)5— Vaso-motor  fibres  to  the 
heart,  206— Vaso-motor  fibres  to  the  intestines,  206— Vaso-motor  fibres  to  the  liver,  206 
— Vaso-motor  nerves  of  the  kidney,  207 — Vaso-motor  nerves  of  the  spleen,  207 — Vaso- 
motor nerves  of  the  pancreas,  207 — Vaso-motor  nerves  of  the  external  generative  organs, 
207 — Vaso-motor  nerves  of  the  internal  generative  organs,  208 — Vaso-motor  nerves  of 
the  portal  system,  209— Vaso-motor  nerves  of  the  limbs,  muscles,  and  tail,  209. 

SECRETION  (By  W.  H.  Howell) >1\\ 

A.  General  Considerations      211 

Definition  of  gland  and  secretion,  211 — Types  of  glandular  structure,  212— Older 

views  of  secretion  and  excretion,  213— General  proofs  that  gland  cells  take  an  active 
part  in  secretion,  214 — Filtration  through  living  and  dead  tissues,  215. 

B.  Mucous  and  Albuminous  Glands— Salivary  Glands 215 

Distinction  between  mucous  and  albuminous  glands,  215— Goblel  cells  as  unicellular 

mucous  glands,  216— Anatomical  relations  of  salivary  glands,  217  Nerve-sapply  to 
salivary  glands,  218 — Histology  of  salivary  glands,  219— Composition  id"  the  saliva, 
220 — Significance  of  the  potassium  sulphocyanide  in  saliva,  221 — Discovery  of  secre 
tory  nerve-fibres  to  the  salivary  glands,  221—  Distinct  ion  between  "chorda"  and 
"sympathetic"  saliva,  222—  Effect  of  varying  the  strength  of  the  stimulus  upon  the 
composition  of  the  saliva,  223 — Theory  of  trophic  and  secretory  fibres,  224  Vacuoles 
in  gland  cells  during  secretion,  226  —Histological  changes  in  glands  as  a  result  of  func- 
tional activity,  226 — Action  of  atropin,  pilocarpin,  and  nicotin  on  secretory  fibres,  229 
— The  normal  mechanism  of  salivary  secretion,  230— Electrical  changes  in  the  salivaVy 
glands  during  secretion,  231. 

C     The  Pancreas — Glands  of  the  Stomach  and    Intestines 231 

Anatomical  relations  of  the  pancreas,  231  Histological  characters  of  the  pancreas, 
231 — Composition  of  the  pancreatic  secretion,  232  -  Secretory  nerves  of  the  pancreas, 
232 — Histological  changes  in  pancreatic  cells  during  secretion,  '.':;::  Distinction 
between  enzymes  and  zymogens,  235  The  normal  mechanism  of  the  pancreatic  Becre- 
tion,  235— The  histological  characteristics  of  the  gastric  glands,  237  Composition  of 
the  gastric  secretion,  238  -Secretory  nerves  of  the  gastric  plan ds,  239  The  normal 
mechanism  of  the  gastric  secretion,  210  Histological  changes  in  the  gastric  glands 
during  secretion,  242 — The  secretion  of  the  intestinal  glands,  243. 

D.  Liver  and  Kidney 244 

Histology  of  liver  in  relation   to  the  bile-ducts,  -J 1 1     Composition  of  the  bile,  215 — 

The  quantity  of  bile  secreted,  246— Relation  of  the  blood-flow  to  the  secretion  of  bile, 
247 — Secretory  nerve-libres  to  the  liver  cells,  217  Motor  innervation  of  the  bile-ducts 
and  gall-bladder,  248— The  normal  mechanism  of  the  bile  secretion,  248  Effect  of 
occlusion  of  the  bile-ducts,  249— Histological  characteristics  of  the  kidney.  249  Com- 
position of  the  urine,  250— General  theories  of  the  secretion  of  urine.  251  Secretion 
of  urea  and  related  nitrogenous  bodies,  252  Secretion  of  the  water  and  salts,  253 — 
The  blood-flow  through  the  kidney  and  its  relations  to  secretion.  255. 


12  CONTENTS. 

PAGE 

E.    Cutaneous  Glands — Internal  Seceetion 257 

Sebaceous  secretion,  257— The  sweat-glands  and  the  quantity  of  their  secretion,  258 
— The  composition  of  sweat.  258  Secretory  fibres  to  the  sweat-glands,  25!) — The  posi- 
tion of  the  sweat-centres  in  the  cord  and  medulla,  26Q— The  structure  and  phylogeny 
of  the  mammary  glands,  261 — Composition  of  the  milk,  261?  Histological  changes  in 
the  mammary  glands  during  secretion,  262 — Secretory  nerve-fibres  to  the  mammary 
glands,  263 — Normal  mcchauism  of  the  secretion  of  milk,  264 — Internal  secretions, 
general  statements,  265  The  internal  secretions  of  the  liver,  265  The  internal  secre- 
tion of  the  pancreas,  266  -The  anatomical  and  histological  relations  of  the  thyroid 
body,  267  Accessory  thyroids,  268  The  anatomical  relations  of  the  parathyroids, 
268  The  functions  of  the  thyroids  and  parathyroids,  268  Effect  of  removal  of  the 
adrenal  bodies,  271 — Action  of  adrenal  extracts  on  the  circulation,  271 — Secretory 
nerves  to  the  adrenals,  272  The  isolation  of  epinephrin,  272— Anatomical  relations 
of  the  pituitary  body,  272— Physiological  effects  of  extracts  of  the  pituitary  body,  272 
— The  internal  secretions  of  the  testis  and  the  ovary,  273. 

CHEMISTRY  OF  DIGESTION  AND  NUTRITION  (By  W.  H.  Howell)  275 

A.  Definition  and  Composition  of  Foods    Characteristics  of  Enzymes  .   .   .   .  275 

General  statements  regarding  foods  and  food-stuffs,  275 — General  nutritive  sig- 
nificance  of  the  food-stuffs,  27<i  Analysis  of  foods,  278 — Definition  and  classification  of 
enzymes,  279— General  reactions  of  the  enzymes,  281 

B.  Salivary  Digestion        283 

Properties   and   composition   of  the   mixed   saliva,  283 — Ptyalin  and  its  action  on 

starch,  2.^4 — Conditions  influencing  the  action  of  ptyalin,  286 — General  functions  of 
saliva,  287. 

C.  Gastric  Digestion 287 

General  conditions  in  the  stomach  during  digestion,  287 — Methods  of  obtaining  gas- 
tric juice,  287 — The  properties  and  composition  of  the  gastric  juice,  288 — The  nature  of 
the  acid  of  the  gastric  juice,  289 — The  theories  as  to  the  origin  of  the  IIC1,  289 — Nature 
and  properties  of  pepsin,  290 — The  preparation  of  an  artificial  gastric  juice,  291 — The 
digestive  action  of  pepsin-hydrochloric  acid,  292 — Definition  of  peptone,  294 — The 
preparation  and  properties  of  rennin,  295 — The  action  of  gastric  juice  on  fats  and  car- 
bohydrates, 296 — Action  of  gastric  juice  on  albuminoids,  297 — Why  does  the  stomach 
not  digest  itself?  297— General  summary  of  the  functions  of  the  stomach,  298. 

D.  Intestinal  Digestion 299 

The  composition  of  pancreatic  juice,  299 — The  properties  and  methods  of  preparing 

trypsin,  301 — The  products  of  tryptic  digestion,  302 — Tryptic  digestion  of  albumin- 
oids, 304 — Amylopsin,  its  occurrence  and  digestive  action,  304 — Steapsin,  its  occur- 
rence and  action  on  fats,  305 — Emulsification  of  fats,  306 — The  intestinal  secretion, 
308 — The  occurrence  and  action  of  the  inverting  enzymes,  308 — Digestion  in  the  large 
intestine,  309— Bacterial  decompositions  in  the  huge  intestine,  309. 

E.  Absorption — Summary  of  Digestion  and  Absorption  of  Food-stuffs — Feces.  311 
General  statement  of  the  conditions  and  products  of  absorption,  311 — Absorption  in 

the  stomach,  312  -Absorption  in  the  stomach  of  water,  salts,  sugars,  peptones,  and 
fats,  313— Absorption  in  the  small  intestine,  313 — Absorption  in  the  large  intestine, 
314 — Absorption  of  proteids,  315 — Absorption  of  sugars,  317 — Absorption  of  fats,  317 — 
Absorption  of  water  and  salts,  318 — Composition  of  the  feces,  319. 

F.  Physiology  of   the  Liver  and  the  Spleen 320 

Histological  arrangement    of  the    liver    lobule,  320 — The  composition  of  bile,  321 — 

The  bile-pigments,  322  -The  bile-acids,  323— Cholesterin,  324  — Lecithin,  fats,  and 
nucleo-albumin  in  bile,  325— General  physiological  importance  of  bile,  325 — Glycogen 
in  the  liver,  326 — The  origin  of  glycogen  with  reference  to  the  food-stuffs,  327 — The 
effect  of  proteids  on  glycogen-formation,  328 — The  effect  of  fats  on  glycogen-formatioa, 
329— The  function  of  glycogen,  and  the  glycogenic  theory,  329— Glycogen  in  the  mus- 
cles and  other  tissues,  330 — Conditions  affecting  the  supply  of  glycogen  in  the  body, 
331 — Formation  of  urea  in  the  liver,  331— Physiology  of  the  spleen,  332. 

<;.    The  Kidney  and  Skin   \s  Excretory  Organs 334 

Genera]  composition  of  the  urine.  334 — The  properties  and  origin  of  urea,  334 — The 
physiological  history  of  uric  acid  and  the  xanthin  bodies,  338 — The  physiological  his- 
tory of  creatinin,  339-  The  physiological  history  of  hippuric  acid,  339— The  conju- 
gated sulphates  in  the  urine,  340  The  physiological  history  of  the  water  and  salts  of 
the  urine,  341 — The  functions  of  the  skin,  :'»11  Sweat  as  an  excretion,  342 — The  seba- 
ceous secretion,  ,">I2     The  excretion  of  the  COa  through  the  skin,  342, 

11.     Body-metabolism-  Nutritive  Value  of  the  Food-stuffs     343 

Determination  of  the  total  metabolism  id"  the  body,  343  Definition  of  nitrogen- 
equilibrium,  344  -Definition  of  carbon- and  general  body-equilibrium,  315 — The  nutri- 
tive importance  of  the  proteids,  345  The  luxus-consumption  idea,  348  The  nutritive 
value  of  albuminoids,  319  The  nutritive  value  of  fats,  350  The  formation  of  fat  in 
the  body,  351  — The  nutritive  value  of  carbohydrates,  353— The  nutritive  value  of 
water  and  salts,  354. 


CONTENTS.  13 

PAGE 

I.    Accessory  Articles  of   Diet— Variations  of  Body-metabolism   under  Dif- 
ferent Conditions — Potential  Energy  of  Food — Dietetics 357 

Accessory  articles  of  diet,  357 — Stimulants,  357 — Condiments,  flavors,  and  meat 
extracts,  359 — Conditions  influencing  body-metabolism,  359 — The  effect  of  muscular 
work  on  metabolism,  359 — Metabolism  during  sleep,  361— The  effect  of  variations  in 
temperature  on  body-metabolism,  362 — The  effect  of  starvation  on  body-metabolism, 
362 — The  potential  energy  of  food,  364 — The  principles  of  dietetics,  366. 

MOVEMENTS  OF  THE  ALIMENTARY  CANAL,  BLADDER,  AND 

URETER  (By  W.  H.  Howell) 369 

The  physiology  of  plain  muscle  tissue,  369 — Mastication,  372 — Deglutition,  372— 
The  Kronecker-Meltzer  theory  of  deglutition,  375 — The  nervous  control  of  degluti- 
tion, 376 — Movements  of  the  stomach,  377 — The  extrinsic  nerves  controlling  the  move- 
ments of  the  stomach,  381 — Movements  of  the  intestines,  3S2 — The  peristaltic  move- 
ments, 382 — Mechanism  of  the  peristaltic  movement,  384 — Pendular  movements  of  the 
intestines,  3*4— Extrinsic  nerves  of  the  intestines,  384 — Effect  of  various  conditions 
on  the  intestinal  movements,  385 — The  mechanism  of  defecation,  386  -The  act  of 
vomiting,  387 — The  nervous  mechanism  of  vomiting,  388 — Micturition,  389 — Move- 
ments of  the  ureters,  389 — Movements  of  the  bladder,  390 — Nervous  control  of  the 
bladder  movements,  392. 

RESPIRATION  (By  Edward  T.  Reichert) 395 

General  statements,  internal  and  external  respiration,  395. 

A.  The  Respiratory  Mechanism  in  Man 395 

Physiological  anatomy  of  the  lungs  and  thorax,  395 — Conditions  of  pressure  within 

the  thorax,  396 — Definition  of  respiration,  inspiration,  and  expiration,  398— Movements 
of  the  diaphragm,  398 — Movements  of  other  muscles  assisting  the  diaphragm,  399— 
Movements  of  the  ribs,  400 — The  function  of  the  intercostal  muscles,  402 — Summary  of 
the  action  of  the  inspiratory  muscles,  405 — Movements  of  expiration,  406 — Summary 
of  the  action  of  the  expiratory  muscles,  407 — Associated  respiratory  movements,  408 
— Intrapulmonary  and  intrathoracic  pressure,  408 — Respiratory  sounds  and  nasal 
breathing,  409. 

B.  The  Gases  in  the  Lungs,  Blood,  and  Tissues 409 

Alterations  in  the  gases  in  the  lungs,  409 — Alterations  in  the  gases  in  the  blood.  411  — 

The  forces  concerned  in  the  diffusion  of  O  and  CO2  in  the  lungs,  412 — The  interchange 
of  O  and  CO2  between  the  alveoli  and  the  blood,  414 — The  tension  of  0  in  the  blood 
and  tissues,  415 — The  tension  of  CO2  in  the  blood  and  tissues,  416 — The  tension  of  N, 
417 — The  forces  producing  the  interchange  of  O  and  CO2  in  the  lungs,  417 — The 
forces  producing  the  interchange  of  O  and  CO2  in  the  tissues,  419 — The  extraction  of 
gases  from  the  blood,  420 — Cutaneous  respiration,  422 — Internal  or  tissue  respira- 
tion, 422. 

C.  The  Rhythm,  Frequency,  and  Depth  of  the  Respiratory  Movements   .    .  423 
The  rhythm  of  the  respiratory  movements,  423 — The  frequency  and   depth  of  the 

respiratory  movements,  425. 

D.  The  Volumes  of  Air,  Oxygen,  and  Carbon  Dioxide  Respired 426 

Normal  volumes  of  air  respired  and  capacity  of  lungs  and  bronchi.  126     The  volumes 

of  O  and  CO2  respired,  428— Conditions  influencing  the  volumes  of  ()  and  COa  respired, 
429— The  respiratory  quotient,  436— Conditions  influencing  the  respiratory  quotient, 
437. 

E.  Principles  of  Ventilation 439 

F.  The  Effects  of  the  Respiration  of  Various  Gases tin 

G.  The  Effects   of   the  Gaseous  Composition   of  the   Blo< \    the    Respi- 

ratory Movements I  pi 

Eupncea,  dyspnoea,  apncea,  and  polypncsa,  440    The  causes  of  apnoea,  441-  The  effect 

of  muscular  activity  on  the  respiratory  movements.  442-  The  conditions  producing 
polypnosa,  443—  The  conditions  producing  dyspnoea,  443 -Asphyxia.  145. 

H.    Artificial  Respiration na 

I.    The  Effects  of  the  Respiratory  Movements  on  the  Circulation    ....   117 
The  effects  of  respiration  on  blood-pressure,  117    The  effects  of  respiration  on  blood- 
flow,  450— The  effects  of  respiration  on   the  pulse,  151     The  effects  of  obstruction  of 
the  air-passages  and  of  the  respiration  of  rarefied  and  compressed  aii  on  the  circula- 
tion, 45l. 

J.     Special  Respiratory  Movements i;, I 

The  movements  in  coughing,  hawking,  sneezing,  laughing,  crying,  sobbing,  sighing, 
etc.,  454. 

K.     The  NERVOUS  Mechanism  of  the  RESPIRATORY   Movements      455 

The  respiratory  centres,  155  The  rhythmic  activity  of  the  respiratory  centre,  158— 
The  afferent  respiratory  nerves,  160     Effects  of  section  and  stimulation  oftbepneumo- 


14  CONTENTS. 

PAGE 

gastric  nerves,  460 — Effects  of  stimulation  of  the  superior  laryngeal  nerve,  462 — Effects 
of  stimulation  of  the  glossopharyngeal  nerve,  462 — Effects  of  stimulation  of  the  tri- 
geminal nerve,  463  Effects  of  stimulation  of  the  cutaneous  nerves,  463 — The  efferent 
respiratory  nerves,  163. 

L.    The  Condition  of  the  Respiratory  Centre  in  the   Fetus 464 

The  reasons  for  the  absence  of  respiratory  movements  in  the  fetus,  464. 

M.    The  Innervation  of  the  Lings 465 

Broncho-constrictor  and  broncho-dilator  fibres,  465 — Vaso-motor  fibres  to  the  lungs, 
466     Summary  of  the  pulmonary  fibres  found  in  the  vagus,  466. 

ANIMAL  HEAT  (By  Edward  T.  Reichert) 467 

A.  Body-temperature 467 

Eomothermous  and  poikilothermous  animals.  467 — Temperatures  of  different  spe- 
cies of  animals,  467 — The  temperature  <>f  the  different  regions  of  the  body,  46s — The 
conditions  affecting  body-temperature,  469 — Temperature  regulation,  473. 

B.  Income  and  Expenditure  of  Heat 474 

The  potential  energy  as  furnished  by  the  food-stuffs,  474 — The  income  of  heat  and 

methods  of  measuring,  475— The  expenditure  of  heat,  476. 

C.  Beat-production  and  Heat-dissipation      477 

(  alorimetry,  477 — The  construction  and  use  of  calorimeters,  478 — Conditions  affect- 
ing heat-production,  482 — Conditions  affecting  heat-dissipation,  485. 

D.  THE  Heat-mkchanism      .    .  489 

The  mechanism  concerned  in  thermogenesis,  489 — The  thermogenic  tissues,  490 — 

The  thermogenic  nerves  and  centres,  490 — The  mechanism  concerned  in  thermolysis, 
494 — Therruotaxis,  495 — Abnormal  thermotaxis,  496 — Post-mortem  rise  of  tempera- 
ture, 497. 

THE  CHEMISTRY  OF  THE  ANIMAL  BODY  (By  Graham  Lusk)    .  499 

A.  The  Non-metallic  Elements 499 

The   preparation,  occurrence,   and    properties   of  hydrogen,   499 — The  preparation, 

occurrence,  and  properties  of  oxygen,  500 — Ozone,  502 — Traube's  theory  of  oxidations 
in  the  body,  502 — Occurrence,  properties,  and  functions  of  water,  503 — Peroxide  of 
hydrogen,  505 — The  preparation,  occurrence,  and  properties  of  sulphur,  sulphuretted 
hydrogen,  sulphurous  and  sulphuric  acids,  505 — Preparation  and  properties  of  chlorine, 
508  -Bromine  and  its  compounds  in  the  body,  508 — Iodine  and  its  compounds  in  the 
body,  509 — Fluorine  and  its  compounds  in  the  body,  510 — Occurrence  and  properties  of 
nitrogen  and  its  compounds,  510 — Occurrence  of  phosphorus,  513 — Phosphorus-pois- 
oning, 513 — Compounds  of  phosphorus,  514 — Phosphorus  in  the  body,  515 — Occurrence 
of  carbon,  516 — Compounds  of  carbon,  517— Metabolism  of  carbon  in  the  body,  518 — 
Properties  and  compounds  of  silicon,  519 — Occurrence  and  properties  of  potassium 
compounds,  519— Potassium  in  the  body,  520 — Occurrence  and  properties  of  sodium 
and  its  compounds,  521 — Occurrence  of  ammonium  carbonate  and  its  fate  in  the  body, 
523 — Occurrence  anil  properties  of  calcium  and  its  compounds,  523 — The  history  of  cal- 
cium in  the  body,  525 — Occurrence  of  strontium  in  the  body,  526 — Occurrence  and  prop- 
erties of  magnesium  compounds,  527 — The  compounds  of  iron  and  its  history  in  the 
metabolism  of  the  body,  528. 

B.  The  Compounds  of  Carbon 531 

The  derivatives  of  methane.  531 — General  formula  and  reactions  of  the  monatomic 

alcohols,  531 — General  formula  and  reactions  of  the  fatty  acids,  532 — The  properties 
and  occurrence  of  methane,  532  -Properties  of  trichlormethane  (chloroform!,  533 — 
The  properties  of  methyl  aldehyde  and  general  properties  of  aldehydes,  533 — Other 
methyl  compounds  and  their  action  in  the  body,  531 — Properties  and  occurrence  of 
formic  acid,  534 — The  properties  of  ethyl  alcohol,  535— The  fate  of  alcohol  in  the 
body,  535  -The  properties  of  ethyl  ether  and  chloral  hydrate,  535  -The  properties  of 
acetic  acid.  536— The  properties  of  aceto-acetic  acid,  537 — The  properties  of  glycocoll 
(amido-acetic  acid  |,  5:;?  The  properties  of  Barcosin,  537 — Propyl  compounds  and  their 
occurrence  in  the  body,  53*  Butyl  compounds  and  their  occurrence  in  the  body,  539 — 
Pentyl  compounds  and  their  occurrence  in  the  body,  539  Acids  containing  more  than 
five  carbon  atoms  (leucin,  palmitin,  etc.),  540 — Amines,  their  structure  and  occurrence, 
541 — The  cyanogen  compounds,  541 — The.  amines  of  the  olefines  [ptomaines,  toxines, 
etc. i,  542 — Occurrence  and  structure  of  taurin,  543 — Occurrence  and  properties  of  the 
biliary  salts.  513 — The  properties  and  occurrence  of  lactic  acid.  545— -The  properties 
and  occurrence  of  cvstein  and  cystin, 546— The  amido-deri  vat  i  ves  of  carbonic  acid 
(urea,  carbamic  acid  .  548  The  properties  and  occurrence  of  urea,  548 — Creatin, 
creatinin,  histidin,  arginin,  550  The  purin  or  alloxuric  bodies  and  bases,  552 — Oxalic, 
succinic,  and  aspartic  acids,  557— The  properties  and  occurrence  of  glycerin  and  its 
compounds,  558 — The  properties  ami  occurrence  of  lecithin,  559 — The  history  of  fats 
in  the  body,  559 — The  properties  of  oleic  acid,  560. 


CONTENTS.  15 

PAGE 

Carbohydrates 561 

The  structure  and  classification  of  carbohydrates,  561 — The  glycoses,  562 — The  di- 
saccharides,  564 — The  cellulose  group  (starch),  5<ir>. 

Benzol  Derivatives,  or  Aromatic  Compounds 568 

The  benzol  ring,  568— Phenol,  its  structure  and  occurrence,  569— Benzoic  acid,  its 
structure  and  occurrence,  569 — Tyrosiu,  its  structure  and  occurrence,  570 — Indol.  its 
structure  and  occurrence,  571 — Epinephrin,  its  structure  and  occurrence,  572 — The 
history  of  the  aromatic  bodies  in  the  urine,  572 — The  structure  and  history  of  inosit, 
573. 

Substances  of  Unknown  Composition 573 

The  properties  and  occurrence  of  haemoglobin  aud  its  compounds,  57:5 — The  bile-pig- 
ments aud  the  melanius,  574 — The  properties  and  occurrence  of  cholesterin,  575 — The 
general  structure  aud  reactions  of  proteids,  575 — The  classification  of  the  proteids, 
576 — The  protamins  and  remarks  upou  the  theoretical  composition  of  the  proteid 
molecule,  580. 

Index 583 


CONTENTS  OF  VOLUME  II. 


THE  GENERAL  PHYSIOLOGY  OF  MUSCLE  AND  NERVE  (By 
Warren  P.  Lombard). 

THE  CENTRAL  NERVOUS  SYSTEM  (By  Henry  H.  Donaldson). 

THE  SPECIAL  SENSES— VISION  (By  Henry  P.  Bowditch). 

HEARING,  CUTANEOUS  AND  MUSCULAR  SENSIBILITY,  EQUI- 
LIBRIUM, SMELL,  AND  TASTE  (By  Henry  Sewall). 

THE  PHYSIOLOGY  OF  SPECIAL  MUSCULAR  MECHANISMS. 
THE  ACTION  OF  LOCOMOTOR  MECHANISMS  (By  War- 
ren P.  Lombard). 

VOICE  AND  SPEECH  (By  Hexry  Sewall). 

REPRODUCTION  (By  Frederic  S.  Lee). 


AN  AMERICAN 

TEXT-BOOK  OF  PHYSIOLOGY. 


I.  INTRODUCTION. 


The  term  "physiology"  is,  in  an  etymological  sense,  synonymous  with 
"  natural  philosophy,"  and  occasionally  the  word  is  used  with  this  significance 
even  at  the  present  day.1  By  common  usage,  however,  the  term  is  restricted 
to  the  liviug  side  of  nature,  and  is  meant  to  include  the  sum  of  our  know- 
ledge concerning  the  properties  of  living  matter.  The  active  substance  of 
which  living  things  are  composed  is  supposed  to  be  fundamentally  alike  in 
structure  in  all  cases,  and  is  commonly  designated  as  protoplasm  {-oioroz,  first, 
and  nXdofxa,  anything  formed).  It  is  usually  stated  that  this  word  was  first 
introduced  into  biological  literature  by  the  botanist  Von  Mold  to  designate 
the  granular  semi-liquid  contents  of  the  plant-cell.  It  seems,  however,  that 
priority  in  the  use  of  the  word  belongs  to  the  physiologist  Purkinje  (1840), 
who  employed  it  to  describe  the  material  from  which  the  young  animal 
embryo  is  constructed.2  In  recent  years  the  term  has  been  applied  indif- 
ferently to  the  soft  material  constituting  the  substance  of  either  animal  or 
plant-cells.  The  word  must  not  be  understood  to  mean  a  substance  of  a 
definite  chemical  nature  or  of  an  invariable  morphological  structure  ;  it  is 
applied  to  any  part  of  a  cell  that  shows  the  properties  of  life,  and  is  therefore 
only  a  convenient  abbreviation  for  the  phrase  "  mass  of  living  matter." 

Living  things  fall  into  two  great  groups,  animals  and  plant's,  and  corre- 
sponding to  this  there  is  a  natural  separation  of  physiology  into  two  sciences,  one 
dealing  with  the  phenomena  of  animal  life,  the  other  with  plant  life.  In  what 
follows  in  this  introductory  section  the  former  of  these  two  divisions  is  chiefly 
considered,  for  although  the  most  fundamental  laws  of  physiology  are,  without 
doubt,  equally  applicable  to  animal  and  vegetable  protoplasm,  nevertheless  the 
Structure  as  well  as  the  properties  of  the  two  forms  of  matter  are  in  some 
respects  noticeably  different,  particularly  in  the  higher  types  of  organisms  in 
each  group.  The  most  striking  contrast,  perhaps,  is  found  in  the  fad  that 
plants   exhibit   a    lesser   degree   of   specialization    in    form    and    function   and 

1  See  Mineral  Physiology  ami  Physiography,  'I'.  Sterry  Hunt,  L886. 

2  O.  Hertwig:    Die  '/Ale  and  die  (,'ewehe,   lS<t.">. 

Vol.  T.— 2  17 


18  I.V    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

a  much  greater  power  of  assimilation.  Owing  to  this  latter  property  the 
plant-cell  is  able,  with  the  aid  of  solar  energy,  to  construct  its  protoplasm 
from  very  simple  forms  of  inorganic  matter,  such  as  water,  carbon  dioxide, 
and  inorganic  salts.  In  this  way  energy  is  stored  within  the  vegetable  cell  in 
the  substance  of  complex  organic  compounds.  Animal  protoplasm,  on  the  con- 
trary, has  comparatively  feeble  synthetic  properties  ;  it  is  characterized  chiefly 
by  its  destructive  power.  In  the  long  run,  animals  obtain  their  food  from  the 
plant  kingdom,  and  the  animal  cell  is  able  to  dissociate  or  oxidize  the  complex 
material  of  vegetable  protoplasm  and  thus  liberate  the  potential  energy  con- 
tained therein,  the  energy  taking  the  form  mainly  of  heat  and  muscular  work. 
We  must  suppose  that  there  is  a  general  resemblance  in  the  ultimate  structure 
of  animal  and  vegetable  living  matter  to  which  the  fundamental  similarity  in 
properties  is  due,  but  at  the  same  time  there  must  be  also  some  common  dif- 
ference in  internal  structure  between  the  two,  and  it  is  fair  to  assume  that 
the  divergent  properties  exhibited  by  the  two  great  groups  of  living  things 
are  a  direct  outcome  of  this  structural  dissimilarity  ;  to  make  use  of  a  figure 
of  speech  employed  by  Bichat,  plants  and  animals  are  cast  in  different  moulds. 

It  is  difficult,  if  not  impossible,  to  settle  upon  any  one  property  that 
absolutely  shall  distinguish  living  from  dead  matter.  Nutrition,  that  is,  the 
power  of  converting  dead  food  material  into  living  substance,  and  repro- 
duction, that  is,  the  power  of  each  organism  to  perpetuate  its  kind  by  the 
formation  of  new  individuals,  are  probably  the  most  fundamental  charac- 
teristics of  living  things;  but  in  some  of  the  specialized  tissues  of  higher 
animals  the  power  of  reproduction,  so  far  as  this  means  mere  multiplication 
li\  cell-division,  seems  to  be  lost,  as,  for  example,  in  the  case  of  the  nerve-eel  1- 
in  the  central  nervous  system  or  of  the  matured  ovum  itself  before  it  is  fertil- 
ized by  the  spermatozoon.  Nevertheless  these  cellular  units  are  indisputably 
living  matter,  and  continue  to  exhibit  the  power  of  nutrition  as  well  as  other 
properties  characteristic  of  the  living  state.  It  is  possible  also  that  the 
power  of  nutrition  may,  under  certain  conditions,  be  held  in  abeyance,  tempo- 
rarily at  least,  although  it  is  certain  that  a  permanent  loss  of  this  property  is 
incompatible  with  the  retention  of  the  living  condition. 

It  is  frequently  said  that  the  most  general  property  of  living  matter  is  its 
irritability.  The  precise  meaning  of  the  term  vital  irritability  is  hard  to 
define.  The  word  implies  the  capability  of  reacting  to  a  stimulus  and  usually 
also  the  assumption  that  in  the  reaction  some  of  the  inner  potential  energy  of 
tin-  living  materia]  is  liberated,  so  that  the  energy  of  the  response  is  many 
time-  greater,  it  may  be,  than  the  energy  of  the  stimulus.     This  la-t    idea  is 

illustrated  by  the  case  of  a  i trading  muscle,  in  which  the  stimulus  acts  as  a 

liberating  force  causing  chemical  decompositions  of  the  substance  of  the  muscle 
with  the  liberation  of  a  comparatively  large  amount  of  energy,  chiefly  in  the 
form  of  heat  or  of  heat  and  work".  It  may  be  remarked  in  passing,  however, 
that  we  are  not  justified  at  present  in  assuming  that  a  similar  liberation  of 
stored  energy  takes  place  in  all  irritable  tissues.  In  the  case  of  nerve-fibres, 
for  instance,   we  have  a  typically  irritable  tissue  which   responds  readily  to 


INTR  OD  UCTION.  1 9 

external  stimuli,  but  as  yet  it  has  not  been  possible  to  show  that  the  forma- 
tion or  conduction  of  a  nerve  impulse  is  accompanied  by  or  dependent  upon  a 

liberation  of  so-called  potential  chemical  energy.  The  nature  of  the  response 
of  irritable  living  matter  is  found  to  vary  with  the  character  of  the  tissue  or 
organism  on  the  one  hand,  and,  so  far  as  intensity  goes  at  least,  with  the 
nature  of  the  stimulus  on  the  other.  Response  of  a  definite  character  to 
appropriate  external  stimulation  may  be  observed  frequently  enough  in 
dead  matter,  and  in  some  cases  the  nature  of  the  reaction  simulates  closely 
some  of  those  displayed  by  living  things.  For  instance,  a  dead  catgut  string 
may  be  made  to  shorten  after  the  manner  of  a  muscular  contraction  by  the 
appropriate  application  of  heat,  or  a  mass  of  gunpowder  may  be  exploded  by 
the  action  of  a  small  spark  and  give  rise  to  a  great  liberation  of  energy  that 
had  previously  existed  in  potential  form  within  its  molecules.  As  regards 
any  piece  of  matter  we  can  only  say  that  it  exhibits  vital  irritability  when  the 
reaction  or  response  it  gives  upon  stimulation  is  one  characteristic  of  living 
matter  in  general  or  of  the  particular  kind  of  living  matter  under  observation ; 
thus,  a  muscle-fibre  contracts,  a  nerve-fibre  conducts,  a  gland-cell  secretes,  an 
entire  organism  moves  or  in  some  way  adjusts  itself  more  perfectly  to  its 
environment.  Considered  from  this  standpoint,  "irritability  menus  only  the 
exhibition  of  one  or  more  of  the  peculiar  properties  of  living  matter  and  can- 
not be  used  to  designate  a  property  in  itself  distinctive  of  living  structure  ; 
the  term,  in  fact,  comprises  nothing  more  specific  or  characteristic  than  is 
implied  in  the  more  general  phrase  vitality.  When  an  amoeba  dies  it  is  no 
longer  irritable,  that  is,  its  substance  no  longer  assimilates  when  stimulated  by 
the  presence  of  appropriate  food,  its  conductivity  and  contractility  disappear 
so  that  mechanical  irritation  no  longer  causes  the  protrusion  or  retraction  of 
pseudopodia — no  form  of  stimulation,  in  fact,  is  capable  of  calling  forth  any 
of  the  recognized  properties  of  living  matter.  To  ascertain,  therefore,  whether 
or  not  a  given  piece  of  matter  possesses  vital  irritability  we  must  first  become 
acquainted  with  the  fundamental  properties  of  living  matter  in  order  to  recog- 
nize the  response,  if  any,  to  the  form  of  stimulation  \\>c(\. 

Nutrition  or  assimilation,  in  a  wide  sense  of  the  word,  has  already  been 
referred  to  as  probably  the  most  universal  and  characteristic  of  these  prop- 
erties. By  this  term  we  designate  that  scries  of  changes  through  which  dead 
matter  is  received  into  the  structure  of  living  substance.  The  term  in  its 
broadest  sense  may  be  used  to  cover  the  subsidiary  processes  of  digestion. 
respiration,  absorption,  and  excretion  through  which  {'<><><{  material  and 
oxygen  are  prepared  for  the  activity  of  the  living  molecules,  and  the  waste 
products  of  activity  are  removed  from  the  organism,  as  well  as  the  actual 
conversion  of  dead  material  into  living  protoplasm.  This  last  act,  which  is 
presumably  a  synthetic  process  effected  under  the  influence  of  living  matter, 
is  especially  designated  as  anabolisni  or  as  assimilation  in  a  narrower  sense 
of  the  word  as  opposed  to  disassimilat ion.  By  disassimilation  or  katabolism 
we  mean  those  changes  leading  to  the  destruction  of  the  complex  substance  of 
the  living  molecules,  or  of  the  food  material  in  contact  with  these  molecules. 


20  AN    AMERICAN    TEXT-HOOK   OF   PHYSIOLOGY. 

As  was  said  before,  animal  protoplasm  is  pre-eminently  katabolic,  and  the 
evidence  of  its  katabolism  is  found  in  the  waste  products,  sucb  as  C02, 
II.O,  and  area,  which  arc  given  off  from  animal  organisms.  Assimilation 
and  disassimilation,  or  anabolism  and  katabolism,  go  hand  in  hand,  and 
together  constitute  an  ever-recurring  cycle  of  activity  that  persists  as  long 
as  the  material  retains  its  living  structure,  and  is  designated  under  the 
name  metabolism.  In  most  forms  of  living  matter  metabolism  is  in  some 
way  self-limited,  so  that  gradually  it  becomes  less  perfect,  old  age  comes  on, 
and  finally  death  ensues.  It  has  been  asserted  that  originally  the  metabolic 
activity  of  protoplasm  was  self-perpetuating — that,  barring  accident,  the  cycle 
of  changes  would  go  on  forever.  Resting  upon  this  assumption  it  has  been 
suggested  by  Weissmann  that  the  protoplasm  of  the  reproductive  elements 
still  retains  this  primitive  and  perfect  metabolism  and  thus  provides  for  the 
continuity  of  life.  The  speculations  bearing  upon  this  point  will  be  discussed 
in  more  detail  in  the  section  on  Reproduction. 

Reproduction  in  some  form  is  also  practically  a  universal  property  of 
living  matter.  The  unit  of  structure  among  living  organisms  is  the  cell. 
Under  proper  conditions  of  nourishment  the  cell  may  undergo  separation  into 
two  daughter  cells.  In  some  cases  the  separation  takes  place  by  a  simple  act 
of  fission,  in  other  cases  the  division  is  indirect  and  involves  a  number  of 
interesting  changes  in  the  structure  of  the  nucleus  and  the  protoplasm  of  the 
body  of  the  cell.  In  the  latter  case  the  process  is  spoken  of  as  karyokinesis 
or  mitosis.  This  act  of  division  was  supposed  formerly  to  be  under  the  con- 
trol of  the  nucleus  of  the  cell,  hut  modern  histology  has  shown  that  in  kary- 
okinetic  division  the  process,  in  many  cases  at  least,  is  initiated  by  a  special 
structure  to  which  the  name  centrosome  has  been  given.  The  many-celled 
animals  arise  by  successive  divisions  of  a  primitive  cell,  the  ovum,  and  in  the 
higher  forms  of  life  the  ovum  requires  to  be  fertilized  by  union  with  a  sper- 
matozoon before  cell-division  becomes  possible.  The  sperm-cell  acts  as  a 
stimulus  to  the  egg-cell  (see  section  on  Reproduction), and  rapid  cell-division 
is  the  result  of  their  union.  It  must  be  noted  also  that  the  term  reproduc- 
tion includes  the  power  of  hereditary  transmission.      The  daughter-cells  are 

similar  in  form  to  the  parent-cell,  and  tl rganism  produced  from  a  fertilized 

ovum  is  substantially  a  facsimile  of  the  parent  forms.  Living  matter,  there- 
fore, not  only  exhibits  the  power  of  separating  off  other  units  of  living  matter, 
but  of  transmitting  to  its  progeny  its  own  peculiar  internal  structure  and 
properties. 

Contractility  and  conductivity  are  properties  exhibited  in  one  form  or 
another  in  all  animal  organisms,  and  we  must  concede  that  they  are  to  be 
counted  among  the  primitive  properties  of  protoplasm.  The  power  of  con- 
tracting or  shortening  is,  in  fact,  one  of  the  commonly  recognized  features  of 
a  living  thing.  It  is  generally  present  in  the  simplest  forms  of  animal  as 
well  as  vegetable  life,  although  in  the  more  specialized  forms  it  is  found  most 
highly  developed  in  animal  organisms.  The  opinion  seems  to  be  general 
among  physiologists  that  wherever  this  property  is  exhibited,  whether  in  the 


INTlt  OD  UCTIO  N.  2 1 

formation  of  the  pseudopodia  of  an  amoeba  or  white  blood-corpuscle,  or  in 
the  vibratile  movements  of  ciliary  structures,  or  in  the  powerful  contractions 
of  voluntary  muscle,  the  underlying  mechanism  by  which  the  shortening  is 
produced  is  essentially  the  same  throughout.  However  general  the  property 
may  be,  it  cannot  be  considered  as  absolutely  characteristic  of  living  struc- 
ture. As  was  mentioned  before,  Engelmann '  has  been  able  to  show  that  a  dead 
catgut  string  when  surrounded  by  water  of  a  certain  temperature  and  exposed 
to  a  sudden  additional  rise  of  temperature  will  contract  or  shorten  in  a  man- 
ner closely  analogous  to  the  contraction  of  ordinary  muscular  tissue,  and  it  is 
not  at  all  impossible  that  the  molecular  processes  involved  in  the  shortening 
of  the  catgut  string  and  the  muscle-fibre  may  be  esseutiallv  the  same. 

That  conductivity  is  also  a  fundamental  property  of  primitive  protoplasmic 
structure  seems  to  be  assured  by  the  reactions  which  the  simple  motile  forms 
of  life  exhibit  when  exposed  to  external  stimulation.  An  irritation  applied 
to  one  point  of  a  protoplasmic  mass  may  produce  a  reaction  involving  other 
parts,  or  indeed  the  whole  extent  of  the  organism.  The  phenomenon  is  most 
clearly  exhibited  in  the  more  specialized  animals  possessing  a  distinct  nervous 
system.  In  these  forms  a  stimulus  applied  to  one  organ,  as  for  instance  light 
acting  upon  the  eve,  may  be  followed  by  a  reaction  involving  quite  distant 
organs,  such  as  the  muscles  of  the  extremities,  and  we  know  that  in  these 
cases  the  irritation  has  been  conducted  from  one  organ  to  the  other  by  means 
of  the  nervous  tissues.  But  here  also  we  have  a  property  that  is  widely 
exhibited  in  inanimate  nature.  The  conduction  of  heat,  electricity,  and  other 
forms  of  energy  is  familiar  to  every  one.  While  it  is  quite  possible  that  con- 
duction through  the  substance  of  living  protoplasm  is  something  mi  generis, 
and  does  not  find  a  strict  parallel  in  dead  structures,  yet  it  must  be  admitted 
that  it  is  conceivable  that  the  molecular  processes  involved  in  nerve  conduction 
may  be  essentially  the  same  as  prevail  in  the  conduction  of  heat  through  a 
solid  body,  or  in  the  conduction  of  a  wave  of  pressure  through  a  liquid  mass. 
At  present  we  know  nothing  definite  as  to  the  exact  nature  of  vital  conduction, 
and  can  therefore  affirm  nothing. 

The  four  great  properties  enumerated,  namely,  nutrition  or  assimilation 
(including  digestion,  secretion,  absorption,  excretion,  anabolism,  and  katabolism), 
reproduction,  conduction,  and  contractility, form  the  important  features  which 
we  may  recognize  in  all  living  things  and  which  we  make  use  of  in  distin- 
guishing between  dead  and  living  matter.  A  fifth  property  perhaps  should 
be  added,  that  of  sensibility  or  sensation,  but  concerning  this  property  as  a 
general  accompaniment  of  living  structure  our  knowledge  is  extremely  im- 
perfect; something  more  as  to  the  difficulties  connected  with  this  subject  will 
•be  said  presently.  The  four  fundamental  properties  mentioned  are  all  ex- 
hibited in  some  degree  in  the  simplest  forms  of  life,  sueli  as  the  protozoa.  In 
the  more  highly  organized  animals,  however,  we  find  thai  specialization  of 
function   prevails.      Hand    in    hand  with   the  differentiation    in    form    that    is 

displayed  in  the  structure  of  tin istituent  tissues  there  goes  a  specialization 

1  Ueber  dt'n  Uraprung  der  Muskelkraft,  Leipzig,  1893. 


22  AN   AMERICAN    TEXT- HOOK   OF  PHYSIOLOGY. 

in  certain  properties  with  a  concomitant  suppression  of  other  properties,  the 
outcome  of  which  is  that  muscular  tissue  exhibits  pre-eminently  the  power  of 
contractility,  the  nerve  tissues  are  characterized  by  a  highly  developed  power 
of  conductivity,  and  so  on.  While  in  the  simple  unicellular  forms  of  animal 
life  the  fundamental  properties  are  all  somewhat  equally  exhibited  within  the 
compass  of  a  single  unit  or  cell,  in  the  higher  animals  we  have  to  deal  with 

a  vast  < linunity  of  cells  segregated  into  tissues  each  of  which  possesses  some 

distinctive  property.  This  specialization  of  function  is  known  technically  as 
the  physiological  division  of  labor.  The  beginning  of  this  process  may  be 
recognized  in  the  cell  itself.  The  typical  cell  is  already  an  organism  of  some 
complexity  as  compared  with  a  simple  mass  of  undifferentiated  protoplasm. 
The  protoplasm  of  the  nucleus,  particularly  of  that  material  iu  the  nucleus 
which  i-  designated  as  chromatin,  is  differentiated,  both  histologically  aud 
physiologically,  from  the  protoplasm  of  the  rest  of  the  cell,  the  so-called  cyto- 
plasm. The  chromatin  material  iu  the  resting  cell  is  arranged  usually  in  a 
network,  but  during  the  act  of  division  (karyokinesis)  it  is  segmented  into  a 
number  of  rods  or  filaments  known  as  chromosomes.  Iu  the  ovum  there  are 
good  reasons  for  believing  that  the  power  of  transmitting  hereditary  charac- 
teristics is  dependent  upon  the  structure  of  these  chromosomes.  The  nucleus, 
moreover,  controls  in  some  way  the  metabolism  of  the  entire  cell,  for  it  has 
been  shown,  iu  some  cells  at  least,  that  a  non-nucleated  piece  of  the  cytoplasm 
is  not  only  deprived  of  the  power  of  reproduction,  but  has  also  such  limited 
powers  of  nutrition  that  it  quickly  undergoes  disintegration.  On  the  other 
hand  contractility  and  conductivity,  and  some  of  the  functions  connected  with 
nutrition,  such  as  digestion  and  excretion,  seem  often  to  be  specialized  iu  the 
cytoplasm.  As  a  further  example  of  differentiation  in  the  cell  itself  the  ex- 
istence of  the  centrosome  may  be  referred  to.  The  centrosome  is  a  body  of 
very  minute  size  that  has  been  discovered  in  numerous  kinds  of  cells.  It 
is  considered  by  many  observers  to  be  a  permanent  structure  of  the  cell,  lying 
either  in  the  cytoplasm,  or  possibly  in  some  discs  within  the  boundaries  of  the 
nucleus.  When  present  it  seems  to  have  some  special  function  in  connection 
with  the  movements  of  the  chromosomes  during  the  act  of  cell-division.  In 
the  many-celled  animals  the  primitive  properties  of  protoplasm  become  highly 
developed,  in  consequence  of  this  subdivision  of  function  among  the  various 
tissues,  and  in  many  ways  the  most  complex  animals  are,  from  a  physiological 
standpoint,  the  simplest  for  purposes  of  study,  since  in  them  the  various  prop-' 
erties  of  living  matter  are  not  only  exhibited  more  distinctly, but  each  is,  as  it 
were,  isolated  from  the  others  and  can  therefore  be  investigated  more  directly. 
We  are  at  liberty  to  suppose  that  the  various  properties  so  clearly  recognizable 
in  the  differentiated  tissues  of  higher  animals  are  all  actually  or  potentially 
contained  in  the  comparatively  undifferentiated  protoplasm  of  the  simplest  uni- 
cellular forms.  That  the  lilies  of  variation,  or  in  other  words  the  direction  of 
specialization  in  form  and  function,  are  not  infinite,  but  on  the  contrary 
comparatively  limited,  seems  evident  when  we  reflect  that  in  spite  of  the 
numerous   branches  of  the  phylogenetic  stem  the  properties    as  well  as  the 


poss 


INTR  OD  UCTION.  21 1 

forms  of  the  differentiated  tissues  throughout  the  animal  kingdom  are  strikingly 
alike.  Striated  muscle,  with  the  characteristic  property  of  sharp  and  powerful 
contraction,  is  everywhere  found;  the  central  nervous  system  in  the  inver- 
tebrates is  built  upon  the  same  type  as  in  the  highest  mammals,  and  the 
variations  met  with  in  different  animals  are  probably  but  varying  degrees  of 
perfection  in  the  development  of  the  innate  possibility  contained  in  primitive 
protoplasm.  It  is  not  too  much  to  say,  perhaps,  that  were  we  acquainted  with 
the  structure  and  chemistry  of  the  ultimate  units  of  living  substance,  the  key 
to  the  possibilities  of  the  evolution  of  form  and  function  would  be  in  our 
ossession. 

Most  interesting  suggestions  have  been  made  in  recent  years  as  to  the 
essentia]  molecular  structure  of  living  matter.  These  views  are  necessarily 
very  incomplete  and  of  a  highly  speculative  character,  and  their  correctness  or 
incorrectness  is  at  present  beyond  the  range  of  experimental  proof;  never- 
theless they  are  sufficiently  interesting  to  warrant  a  brief  statement  of  some 
of  them,  as  they  seem  to  show  at  least  the  trend  of  physiological  thought. 

Pfliiger,1  in  a  highly  interesting  paper  upon  the  nature  of  the  vital  pro- 
cesses, calls  attention  to  the  great  instability  of  living  matter.  He  supposes 
that  living  substance  consists  of  very  complex  and  very  unstable  molecules  of 
a  proteid  nature  which,  because  of  the  active  intra-molecular  movement  pre- 
sent, are  continually  dissociating  or  falling  to  pieces  with  the  formation  of 
simpler  and  more  stable  bodies  such  as  water,  carbon  dioxide  and  urea,  the  act 
of  dissociation  giving  rise  to  a  liberation  of  energy.  "  The  intra-molecular 
heat  (movement)  of  the  cell  is  its  life."  He  suggests  that  in  this  living  mole- 
cule the  nitrogen  is  contained  in  the  form  of  a  cyanogen  compound,  and  that 
the  instability  of  the  molecule  depends  chiefly  upon  this  particular  grouping. 
Moreover  the  power  of  the  molecule  to  assimilate  dead  proteid  and  convert  it  to 
living  proteid  like  itself  he  attributes  to  the  existence  of  the  cyanogen  group. 
It  is  known  that  cyanogen  compounds  possess  the  property  of  polymerization, 
that  is,  of  combining  with  similar  molecules  to  form  more  complex  mole- 
cules, and  we  may  suppose  that  the  molecules  of  dead  proteid  when  brought 
into  contact  with  the  living  molecules  are  combined  with  the  latter  by  a  pro- 
cess analogous  to  polymerization  or  condensation.  By  this  means  the  stable 
structure  of  dead  proteid  is  converted  to  the  labile  structure  of  living  proteid, 
and  the  molecules  of  the  latter  increase  in  size  and  instability.  When  living 
substance  dies  its  molecules  undergo  alteration  and  become  incapable  of  ex- 
hibiting the  usual  properties  of  life.  Pfliiger  suggests  that  the  change  may 
consist  essentially  in  an  absorption  of  water  whereby  the  cyanogen  grouping 
passes  over  into  an  ammonia  grouping.  Loew2  assumes  also  that  the  dif- 
ference between  dead  and  living  or  active  proteid  lies  chiefly  in  the  fact  thai 
in  the  latter  we  have  a  very  unstable  or  labile  molecule  in  which  the  atoms  are 
in  active  motion.     The  instability  of  the  molecules  he   likewise  attributes  to 

1  Archiv  fur  die  gesammte  Physiologie,  1ST"),  I'd.  lo.  S.  251. 

2  Ibid.,  1880,  Bd.  22;  Loew  and  Bokorny:  Die  chemische  Kraftquelh  in  lebenden  Protoplasma, 
Miinchen,  1882;  Imperial  Institute  of  Tokyo  (College  of  Agriculture),  1894. 


24  AN  AMERICA X    TEXT-BOOK    OF  PHYSIOLOGY. 

the  existence  of  certain  groupings  of  the  atoms.  Influenced  in  part  by  the 
power  of  living  material  to  reduce  alkaline  silver  solutions,  he  supposes  that 
the  specially  important  labile  group  in  the  molecule  is  the  aldehyde  radical 

—  C  ~  it  •     The  nitrogen  exists  also  in  a  labile  amido-  combination,  — NH2, 

and  the  active  or  living  form  of  these  two  groups  may  be  expressed  by  the 

-CH-NH2 
formula  Q.     11  this  grouping  by  chemical  change  became  con- 

=  c  -c    j, 

f  1TT  VII 

verted  to  the  grouping  __   ^    —  PHOH'  li  wou^  ^orm  a  comparatively  inert 

compound  such  as  we  have  in  dead  proteid.  Latham1  proposes  a  theory 
which  combines  the  ideas  of  Pfliiger  and  of  Loew.  He  suggests  that  the 
living  molecule  may  be  composed  of  a  chain  of  cyan-alcohols  united  to  a  ben- 
zene nucleus.  The  cyan-alcohols  are  obtained  by  the  union  of  an  aldehyde 
with  hydrocyanic  acid  ;  they  contain,  therefore,  the  labile-aldehyde  grouping 
as  well  as  the  cyanogen   nucleus  to  which  Pfliiger  attributes  such  importance. 

Actual  investigation  of  the  chemical  structure  of  living  matter  can  hardly 
be  said  to  have  made  a  beginning.  The  first  step  in  this  direction  has  been 
made  in  the  study  of  the  chemical  structure  of  the  group  of  proteids  which 
have  usually  been  considered  as  forming  the  most  characteristic  constituent 
of  protoplasm.  Proteids  as  we  obtain  them  from  the  dead  tissues  and  liquids 
of  the  body  have  proved  to  be  very  varied  in  properties  and  structure,  so 
much  so  in  fact  that  it  is  impossible  to  give  a  satisfactory  definition  of  the 
group.  Man)  of  them  can  be  obtained  in  a  pure,  even  in  a  crystalline  form, 
and  their  percentage  composition  can  therefore  be  determined  with  ease. 
But  the  fundamental  chemical  structure  that  may  be  supposed  to  characterize 
the  proteid  group,  and  the  changes  in  this  structure  producing  the  different 
varieties  of  proteids  are  matters  as  yet  undetermined.  Several  promising 
efforts  have  been  made  to  construct  proteids  synthetically,  but  the  results 
obtained  are  at  present  incomplete.  On  the  other  hand,  Kossel 2  has  isolated 
from  the  spermatozoa  of  certain  fishes  a  comparatively  simple  nitrogenous 
body  of  basic  properties  (protamine),  which  he  regards  as  the  simplest  form 
of  pndeid  and  the  essential  cure  or  nucleus  characterizing  the  structure  of  the 
whole  group.  It  is  an  interesting  thought  that  in  the  heads  of  the  sperma- 
tozoa with  their  complex  possibilities  of  development  and  hereditary  trans- 
mission,  dependent  as  these  properties  must  be  upon  the  chemical  structure 
of  the  germ  protoplasm,  there  may  be  found  the  simplest  form  of  proteid. 
Kossel's  work,  it  may  be  noted,  has  not  gone  so  far  as  to  indicate  the  possible 
molecular  structure  of  the  protamines. 

It  has  been  assumed  by  many  observers  that  the  properties  of  living 
matter,  as  we  recognize  them,  are  not  solely  an  outcome  of  the  inner  structure 
of  the  hypothetical  living  molecules.     They  believe  that  these  latter  units  are 

1  British  Medical  Journal,  1886,  p.  629. 
Zeitschrift fur  physiol.  Chem.,  1898;  xxv.   L899,  xxvi. 


INTR  OD  UCTION.  2  5 

fashioned  into  larger  secondary  units  each  of  which  is  a  definite  aggregate  of 
chemical  molecules  and  possesses  certain  properties  or  reactions  that  depend 
upon  the  mode  of  arrangement.  The  idea  is  similar  to  that  advanced  by 
mineralogists  to  explain  the  structure  of  crystals.  They  suppose  that  the 
chemical  molecules  are  arranged  in  larger  or  smaller  groups  to  which  the 
name  "physical  molecules"  has  been  given.  So  in  living  protoplasm  it  may 
be  that  the  smallest  particles  capable  of  exhibiting  the  essential  properties 
of  life  are  groups  of  ultimate  molecules,  in  the  chemical  sense,  having  a 
definite  arrangement  and  definite  physical  properties.  These  secondary  units 
of  structure  have  been  designated  by  various  names  such  as  "  physiological 
molecules,"1  "somacules,"2  micellae,3  etc.  Many  facts,  especially  from  the 
side  of  plant  physiology,  teach  us  that  the  physical  constitution  of  protoplasm 
is  probably  of  great  importance  in  understanding  its  reaction  to  its  environ- 
ment. Microscopic  analysis  is  insufficient  to  reveal  the  existence  or  character 
of  these  "  physiological  molecules,"  but  it  has  abundantly  shown  that  proto- 
plasm has  always  a  certain  physical  construction  and  is  not  merely  a  struc- 
tureless fluid  or  semi-fluid  mass. 

What  has  been  said  above  may  serve  at  least  to  indicate  the  prevalent 
physiological  belief  that  the  phenomena  shown  by  living  matter  are  in  the 
11  i;i in  the  result  of  the  action  of  the  known  forms  of  energy  through  a  substance 
of  a  complex  and  unstable  structure  which  possesses,  moreover,  a  physical 
organization  responsible  for  some  of  the  peculiarities  exhibited.  In  other 
words,  the  phenomena  of  life  are  referred  to  the  physical  and  chemical  struc- 
ture of  protoplasm  and  maybe  explained  under  the  general  physical  and 
chemical  laws  which  control  the  processes  of  inanimate  nature.  Just  as  in 
the  case  of  dead  organic  or  inorganic  substances  we  attempt  to  explain  the 
differences  in  properties  between  two  substances  by  reference  to  the  difference 
in  chemical  and  physical  structure  between  the  two,  so  with  regard  to  living 
matter  the  peculiar  differences  in  properties  that  separate  them  from  dead 
matter,  or  for  that  matter  the  differences  that  distinguish  one  form  of  living- 
matter  from  another,  must  eventually  depend  upon  the  nature  of  the  under- 
lying physical  and  chemical  structure. 

In  the  early  part  of  this  century  many  prominent  physiologists  were  still 
so  overwhelmed  with  the  lnvsteriousness  of  life  that  they  took  refuge  in  the 
hypothesis  of  a  vital  force  or  principle  of  life.  By  this  term  was  meant  a 
something  of  an  unknown  nature  that  controlled  all  the  phenomena  ex- 
hibited by  living  things.  Even  ordinary  chemical  compounds  of  a  so-called 
organic  nature  were  supposed  to  be  formed  under  the  influence  of  this  force, 
and  it  was  thought  could  not  be  produced  otherwise.  The  error  of  this  latter 
view  has  been  demonstrated  conclusively  within  recent  years :  many  of  the 
substances  formed  by  the  processes  of  plant  and  animal  life  are  now  easily 
produced  within  the  laboratory  by  comparatively  simple  synthetic  methods. 

1  Meltzer :  "  Ueber  die  fundamentale  Bedeutung  der  Erechiitterung  fur  die  lebende  Ma- 
terie,"  Zeitschrift  fur  Biologie,  Bd.  xxx.,  1894. 

-Foster:  Physiology  (Introduction).         sNSgeli:   Theorieder  Oahrung,  Miinchen,  1879. 


26  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

By  the  distinguished  labors  of  Kinil  Fischer1  even  the  structure  of  carbohy- 
drate bodies  lias  been  determined,  and  bodies  belonging  to  this  group  have 
been  synthetically  constructed  in  the  laboratory.  Moreover,  the  work  of 
Schiitzenberger,  Grimaux,  and  Pickering  gives  promise  that  before  long  pro- 
teid  bodies  may  be  produced  by  similar  methods.  Physiologists  have  shown, 
furthermore,  that  the  digestion  that  takes  place  in  the  stomach  or  intestine 
may  be  effected  also  in  test-tubes,  and  at  the  present  day  probably  no  one 
doubts  that  in  the  act  of  digestion  we  have  to  deal  only  with  a  series  of 
chemical  reactions  which  in  time  will  be  understood  as  clearly  as  it  is  possible 
to  comprehend  any  form  of  chemical  activity.  Indeed,  the  whole  history  of 
food  in  the  body  follows  strictly  the  great  physical  law-  of  the  conservation 
of  matter  and  of  energy  which  prevail  outside  the  body.  No  one  disputes 
the  proposition  that  the  material  of  growth  and  of  excretion  comes  entirely 
from  the  food.  It  has  been  demonstrated  that  the  measureable  energy  given 
off  from  the  body  is  all  contained  potentially  within  the  food  that  is  eaten.2 
Living  things,  so  far  as  can  be  determined,  can  only  transform  matter  and  en- 
ergy ;  they  cannot  create  or  destroy  them,  and  in  this  respect  they  are  like  inan- 
imate objects.  But,  in  spite  of  the  triumphs  that  have  followed  the  use  of  the 
experimental  method  in  physiology,  every  one  recognizes  that  our  knowledge 
is  as  yet  very  incomplete.  Many  important  manifestations  of  life  cannot  be 
explained  by  reference  to  any  of  the  known  facts  or  laws  of  physics  and 
chemistry,  and  in  some  cases  these  phenomena  are  seemingly  removed  from 
the  field  of  experimental  investigations.  As  long  as  there  is  this  residuum 
of  mystery  connected  with  any  of  the  processes  of  life,  it  is  but  natural  that 
there  should  be  two  points  of  view.  Most  physiologists  believe  that  as 
our  knowledge  and  skill  increase  these  mysteries  will  be  explained,  or  rather 
will  be  referred  to  the  same  great  final  mysteries  of  the  action  of  matter  and 
energy  under  definite  laws,  under  which  we  now  classify  the  phenomena  of 
lifeless  matter.  Others,  however,  find  the  difficulties  too  great, — they  perceive 
that  the  laws  of  physics  and  chemistry  are  not  completely  adequate  at  present 
to  explain  all  the  phenomena  of  life,  and  assume  that  they  never  will  be. 
They  suppose  that  there  is  something  in  activity  in  living  matter  which  is 
not  present  in  dead  matter,  and  which  for  want  of  a  better  term  may  be  desig- 
nated as  vital  force  or  vital  energy.  However  this  may  be,  it  seems  evident 
that  a  doctrine  of  this  kind  stifles  inquiry.  Nothing  is  more  certain  than  the 
fact  that  the  great  advances  made  in  physiology  during  the  last  four  decades 
are  mainly  owing  to  the  abandonment  of  this  idea  of  an  unknown  vital  force 
and  the  determination  on  the  part  of  experimenters  to  make  the  greatest  pos- 
sible use  of  the  known  laws  of  nature  in  explaining  the  phenomena  of  life. 
There  is  n<>  reason  to-day  to  suppose  that  we  have  exhausted  the  results  to  be 
obtained  by  the  application  of  the  methods  of  physics  and  chemistry  to  the 
study  of'  living  things,  and  as  a  matter  of  fact  the  great  bulk  of  physiological 
research  is  proceeding  along  these  lines.      It  is  interesting,  however,  to  stop 

1  Die  Chemieder  Kohlenhydrale,  Berlin,  1S94. 
2Kubner :  Tkitschrift fur  Biologic,  Bd.  xxx.  8.  73,  1894. 


INTRODUCTION.  27 

for  a  moment  to  examine  briefly  some  of  the  problems  which  as  yet  have 
escaped  satisfactory  solution  by  these  methods. 

The  phenomena  of  secretion  and  absorption  form  important  parts  of  the 
digestive  processes  in  higher  animals,  and  without  doubt  are  exhibited  in  a 
minor  degree  in  the  unicellular  types.  In  the  higher  animals  the  secretions  may 
be  collected  and  analyzed,  and  their  composition  may  be  compared  with  that 
of  the  lymph  or  blood  from  which  they  are  derived.  It  has  been  found  that 
secretions  may  contain  entirely  new  substances  not  found  at  all  in  the  blood, 
as  for  example  the  mucin  of  saliva  or  the  ferments  and  HC1  of  gastric  juice; 
or,  on  the  other  hand,  that  they  may  contain  substances  which,  although  pres- 
ent in  the  blood,  are  found  in  much  greater  percentage  amounts  in  the  secre- 
tion— as,  for  instance,  is  the  case  with  the  urea  eliminated  in  the  urine.  In  the 
latter  case  we  have  an  instance  of  the  peculiar,  almost  purposeful,  elective 
action  of  gland-cells  of  which  many  other  examples  might  be  given.  With 
regard  to  the  new  material  present  in  the  secretions,  it  finds  a  sufficient  general 
explanation  in  the  theory  that  it  arises  from  a  metabolism  of  the  protoplasmic 
material  of  the  gland-cell.  It  offers,  therefore,  a  purely  chemical  problem 
which  may  and  probably  will  be  worked  out  satisfactorily  for  each  secretion. 
The  selective  power  of  gland-cells  for  particular  constituents  of  the  blood  is 
a  more  difficult  question.  We  find  no  exact  parallel  for  this  kind  of  action 
in  chemical  literature,  but  there  can  be  no  reasonable  doubt  that  the  phe- 
nomenon is  essentially  a  chemical  or  physical  reaction  involving  the  activity 
of  some  of  the  forms  of  energy  with  which  the  study  of  inanimate  objects  has 
already  made  us  partially  familiar.  We  may  indulge  the  hope  that  the  details 
of  the  reaction  will  be  discovered  by  more  complete  chemical  and  micro- 
scopical study  of  the  structure  of  these  cells.  If  in  the  meantime  the  act  of 
selection  is  spoken  of  as  a  vital  phenomenon,  it  is  not  meant  thereby  that  it  is 
referred  to  the  action  of  an  unknown  vital  force,  but  only  that  it  is  a  kind  of 
action  dependent  upon  the  living  structure  of  the  cell-substance. 

The  act  of  absorption  of  digested  products  from  the  alimentary  canal  was 
for  a  time  supposed  to  be  explained  completely  by  the  laws  of  imbibition, 
diffusion,  and  osmosis.  The  epithelial  lining  and  its  basement  membrane  form 
a  septum  dividing  the  blood  and  lymph  on  the  one  side  from  the  contents  of 
the  alimentary  canal  on  the  other.  Inasmuch  as  the  two  liquids  in  question 
;irc  of  unequal  composition  with  regard  to  certain  constituents,  a  diffusion 
stream  should  be  set  up  whereby  the  peptones,  sugar,  salts,  etc.  would  pass 
from  the  liquid  in  the  alimentary  canal,  where  they  exist  in  greater  concen- 
tration, into  the  blood,  where  the  concentration  is  less.  Careful  work  of 
recent  years  has  shown  that  the  laws  of  diffusion  and  osmosis  are  not  adequate 
to  explain  fully  the  absorption  that  actually  occurs;  a  more  detailed  account 
of  the  difficulties  met  with  may  be  found  in  the  section  on  Digestion  and 
Nutrition.  It  has  become  customary  to  speak  of  absorption  as  caused  in  part 
by  the  physical  laws  of  diffusion  and  osmosis,  and  in  pari  by  the  vital  activity 
of  the  epithelial  cells.  It  will  be  noticed  that  the  vital  property  in  this  case  is 
again  an  elective  affinity  for  certain  constituents  similar  to  that  which  has  been 


28  AN  AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

referred  to  in  discussing  the  act  of  secretion.  The  mere  fact  that  the  physical 
theory  has  proved  so  far  to  be  insufficient  is  in  itself  no  reason  for  abandoning 
all  hope  of  a  satisfactory  explanation.  Most  physiologists  probably  believe  that 
further  experimental  work  will  bring  this  phenomenon  out  of  its  obscurity 
and  show  that  it  is  explicable  in  terms  of  known  physical  and  chemical  forces 
exerted  through  the  peculiar  substance  of  the  absorptive  cell. 

The  facts  of  heredity  and  consciousness  offer  difficulties  of  a  much  graver 
character.  The  function  of  reproduction  is  two-sided.  In  the  first  place 
there  is  an  active  multiplication  of  cells,  beginning  with  the  segmentation  of 
the  ovum  into  two  blastomeres,  and  continuing  in  the  larger  animals  to  the 
formation  of  an  innumerable  multitude  of  cellular  units.  In  the  second  place 
there  is  present  in  the  ovum  a  form-building  power  of  such  a  character  that 
the  great  complex  of  eel  Is  arising  from  it  produces  not  a  heterogeneous  mass,  but 
a  definite  organism  of  the  same  structure,  organ  for  organ  and  tissue  for  tissue, 
as  the  parent  form.  The  ovum  of  a  starfish  develops  into  a  starfish,  the 
ovum  of  a  dog  into  a  dog,  and  the  ovum  of  man  into  a  human  being. 
Herein  lies  the  great  problem  of  heredity.  The  mere  multiplication  of  cells 
by  direct  or  indirect  division  is  not  beyond  the  range  of  a  conceivable  me- 
chanical  explanation.  Given  the  properties  of  assimilation  and  contractility  it 
is  possible  that  the  act  of  cell-division  may  be  traced  to  purely  physical  and 
chemical  causes,  and  already  cytological  work  is  opening  the  way  to  credible 
hypotheses  of  this  character.  But  the  phenomena  of  heredity,  on  the  other 
hand,  are  too  complex  and  mysterious  to  justify  any  immediate  expectation 
that  they  can  be  explained  in  terms  of  the  known  properties  of  matter.  The 
crude  theories  of  earlier  times  have  not  stood  the  test  of  investigation  by 
modern  methods,  the  microscopic  anatomy  of  both  ovum  and  sperm  showing 
that  they  are  to  all  appearances  simple  cells  that  exhibit  no  visible  signs  of 
the  wonderful  potentialities  contained  within  them.  Histological  and  experi- 
mental investigation  has,  however,  cleared  away  some  of  the  difficulties  for- 
merlv  surrounding  the  subject,  for  it  has  shown  with  a  high  degree  of  prob- 
ability that  the  power  of  hereditary  transmission  resides  in  a  particular  sub- 
stance in  the  nucleus,  namely  in  the  so-called  chromatin  materal  that  forms 
the  chromosomes.  The  fascinating  observations J  that  have  led  to  this  con- 
clusion promise  to  open  up  a  new  field  of  experimentation  and  speculation. 
It  seems  to  be  possible  to  study  heredity  by  accepted  scientific  methods,  and 
we  may  therefore  hope  that  in  time  more  light  will  be  thrown  upon  the  con- 
ditions of  its  existence  and  possibly  upon  the  nature  of  the  forces  concerned 
in  it>  production. 

In  the  facts  of  consciousness,  lastly,  we  are  confronted  with  a  problem 
seemingly  more  difficult  than  heredity.  In  ourselves  we  recognize  different 
states  of  consciousness  following  upon  the  physiological  activity  of  certain 
parts  of  the  central  nervous  system.  We  know,  or  think  we  know,  that  these 
so-called  psychical  state-  are  correlated  with  changes  in  the  protoplasmic 
material  of  the  cortical  cells  of  the  cerebral  hemispheres.  When  these  cells 
'Wilson:  Tht  Cell  in  Development  and  Inheritance,  1896. 


INTRODUCTION.  29 

are  stimulated,  psychical  states  result;  when  they  are  injured  or  removed, 
psychical  activity  is  depressed  or  destroyed  altogether  according  to  the  extent 
of  the  injury.  From  the  physiological  standpoint  it  would  seem  to  be  as 
justifiable  to  assert  that  consciousness  is  a  property  of  the  cortical  nerve-cells 
as  it  is  to  define  contractility  as  a  property  of  muscle-tissue.  But  the  short- 
ening of  a  muscle  is  a  physical  phenomenon  that  can  be  observed  with  the 
senses — be  measured  and  theoretically  explained  in  terms  of  the  known  prop- 
erties of  matter.  Psychical  states  are,  however,  removed  from  such  methods  of 
study ;  they  are  subjective,  and  cannot  be  measured  or  weighed  or  otherwise  esti- 
mated with  sufficient  accuracy  and  completeness  in  terms  of  our  units  of  energy 
or  matter.  There  must  be  a  causative  connection  between  the  objective  changes 
in  the  brain-cells  and  the  corresponding  states  of  consciousness,  but  the  nature 
of  this  connection  remains  hidden  from  us ;  and  so  hopeless  does  the  problem 
seem  that  some  of  our  profouudest  thinkers  have  not  hesitated  to  assert  that  it 
can  never  be  solved.  Whether  or  not  consciousness  is  possessed  by  all  animals 
it  is  impossible  to  say.  In  ourselves  we  know  that  it  exists,  and  we  have 
convincing  evidence,  from  their  actions,  that  it  is  possessed  by  many  of  the 
higher  animals.  But  as  we  descend  in  the  scale  of  animal  forms  the  evidence 
becomes  less  impressive.  It  is  true  that  even  the  simplest  forms  of  animal 
life  exhibit  reactions  of  an  apparently  purposeful  character  which  some  have 
explained  upon  the  simple  assumption  that  these  animals  are  endowed  with 
consciousness  or  a  psychical  power  of  some  sort.  All  such  reactions,  however, 
may  be  explained,  as  in  the  case  of  reflex  actions  from  the  spinal  cord,  upon 
purely  mechanical  principles,  as  the  necessary  response  of  a  definite  physical 
or  chemical  mechanism  to  a  definite  stimulus.  To  assume  that  in  all  cases  of 
this  kind  conscious  processes  are  involved  amounts  to  making  psychical  activity 
one  of  the  universal  and  primitive  properties  of  protoplasm  whether  animal 
or  vegetable,  and  indeed  by  the  same  kind  of  reasoning  there  would  seem  to 
be  no  logical  objection  to  extending  the  property  to  all  matter  whether  living 
or  dead.  All  such  views  are  of  course  purely  speculative.  As  a  matter  of 
fact  we  have  no  means  of  proving  or  disproving,  in  a  scientific  sense,  the  exist- 
ence of  consciousness  in  lower  forms  of  life.  To  quote  an  appropriate  remark 
of  Huxley's  made  in  discussing  this  same  point  with  reference  to  the  crayfish, 
"  Nothing  short  of  being  a  crayfish  would  give1  us  positive  assurance  that  such 
an  animal  possesses  consciousness."  The  study  of  psychical  states  in  our- 
selves, for  reasons  which  have  been  suggested  above,  does  not  usually  form 
a  part  of  the  science  of  physiology.  The  matter  has  been  referred  to  lure 
simply  because  consciousness  is  a  fact  that  our  science  cannot  :is  yet  explain. 

So  far,  some  of  the  broad  principles  of  physiology  have  been  considered — 
principles  which  are  applicable  with  more  or  less  modification  to  all  forms  of 
animal  life  and  which  make  the  basis  of  what  is  known  as  general  physiology. 
It  must  be  borne  in  mind,  however,  that  each  particular  organism  possesses 
a  special  physiology  of  its  own,  which  consists  in  part  in  a  study  of  the 
properties  exhibited  by  the  particular  kinds  or  variations  of  protoplasm 
in  each  individual,  and  in  large   part   also  in  a  study  of  the  various  median- 


30  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

isms  existing  in  each  animal.  In  the  higher  animals,  particularly,  the  com- 
binations of  various  tissues  and  organs  into  complex  mechanisms  such  as 
those  ol*  respiration,  circulation,  digestion,  or  vision,  differ  more  or  less  in 
each  group  and  to  a  minor  extent  in  each  individual  of  any  one  species.  It 
follows,  therefore,  that  each  animal  has  a  special  physiology  of  its  own,  and 
in  this  sense  we  may  speak  of  a  special  human  physiology.  It  need 
scarcely  be  -aid  that  the  special  physiology  of  man  is  very  imperfectly  known. 
Books  like  the  present  one,  which  profess  to  neat  of  human  physiology,  con- 
tain in  reality  a  large  amount  of  general  and  special  physiology  that  has 
been  derived  from  the  study  of  lower  animal  forms  upon  which  exact  experi- 
mentation is  possible.  Most  of  our  fundamental  knowledge  of  the  physiology 
of  the  heart  and  of  muscles  and  nerves  has  been  derived  from  experiments 
upon  frogs  and  similar  animals,  and  much  of  our  information  concerning  the 
mechanisms  of  circulation,  digestion,  etc.  has  been  obtained  from  a  study  of 
other  mammalian  forms.  We  transfer  this  knowledge  to  the  human  being,  and 
in  general  without  serious  error,  since  the  connection  between  man  and  related 
mammalia  is  as  close  on  the  physiological  as  it  is  on  the  morphological  side, 
and  the  fundamental  or  general  physiology  of  the  tissues  seems  to  be  every- 
where the  same.  Gradually,  however,  the  material  for  a  genuine  special 
human  physiology  is  being  acquired.  In  many  directions  special  investigation 
upon  man  is  possible;  for  instance,  in  the  study  of  the  localization  of  function 
in  the  cerebral  cortex,  or  the  details  of  body  metabolism  as  obtained  by  exam- 
ination of  the  excreta,  or  the  peculiarities  of  vaso-motor  regulation  as  revealed 
by  the  use  of  plethysmography  methods,  or  the  physiological  optics  of  the 
human  eye.  This  special  information,  as  rapidly  as  it  is  obtained,  is  incorpo- 
rated into  the  text-books  of  human  physiology,  but  the  fact  remains  that  the 
greater  part  of  our  so-called  human  physiology  is  founded  upon  experiments 
upon  the  lower  aninals. 

Physiology  as  a  science  is  confessedly  very  imperfect;  it  cannot  compare  in 
exactness  with  the  sciences  of  physics  and  chemistry.  This  condition  of  affairs 
need  excite  no  surprise  when  we  remember  the  very  wide  field  that  physiology 
attempts  to  cover,a  held  co-ordinate  in  extent  with  the  physics  as  well  as  the 
chemistry  of  dead  matter,  and  the  enormous  complexity  and  instability  of  the 
form  of  matter  that  it  seeks  to  investigate.  The  progress  of  physiology  is 
therefore  comparatively  slow.  The  present  era  seems  to  be  one  mainly  of 
accumulation  of  reliable  data  derived  from  laborious  experiments  and  observa- 
tions. The  synthesis  of  these  facts  into  great  laws  or  generalizations  is  a  task 
l.ir  i lie  future.  Corresponding  with  the  diversity  of  the  problems  to  be 
solved  we  find  that  the  methods  employed  in  physiological  research  are  mani- 
fold in  character.  Inasmuch  as  animal  organisms  are  composed  either  of 
single  cells  or  aggregates  of  cells,  it  follows  that  every  anatomical  detail  with 
regard  to  the  organization  of  the  cell  itself  or  the  connection  between  dif- 
fered cells,  and  every  advance  in  our  knowledge  of  the  arrangement  of  the 
tissues  and  organs  that  form  the  re  complicated  mechanisms,  is  of  imme- 
diate value  to  phvsiology.     The  microscopic  anatomy  of  the  cell  (a  branch  of 


I  ST  HO  DICTION.  31 

histology  that   is  frequently  designated  by  the  specific  name  of  cytology), 

general  histology,  and  gross  anatomical  dissection  arc  therefore  frequently 
employed  in  physiological  investigations,  and  form  what  may  be  called  the 
observational  side  of  the  science.  On  the  other  hand,  we  have  the  experimental 
methods,  that  seek  to  discover  the  properties  and  functional  relationships  of 
the  tissues  and  organs  by  the  use  of  direct  experiments.  These  experiments 
may  be  of  a  surgical  character,  involving  the  extirpation  or  destruction  or 
alteration  of  known  parts  by  operations  upon  the  living  animal,  or  they 
may  consist  in  the  application  of  the  accepted  methods  of  physics  and 
chemistry  to  the  living  organism.  The  physical  methods  include  the  study  of 
the  physical  properties  of  living  matter  and  the  interpretation  of  its  activity 
in  terms  of  known  physical  laws,  and  also  the  use  of  various  kinds  of  physical 
apparatus  such  as  manometers,  galvanometers,  etc.  for  recording  with  accuracy 
the  phenomena  exhibited  by  living  tissues.  The  chemical  methods  imply  the 
application  of  the  synthetic  and  analytic  operations  of  chemistry  to  the  study  of 
the  composition  and  structure  of  living  matter  aud  the  products  of  its  activity. 
The  study  of  the  subjective  phenomena  of  conscious  life — in  fact,  the  whole 
question  of  the  psychic  aspects  or  properties  of  living  matter — for  reasons 
that  have  been  mentioned  is  not  usually  included  in  the  science  of  physiol- 
ogy, although  strictly  speaking  it  forms  an  integral  part  of  the  subject.  This 
province  of  physiology  has,  however,  been  organized  into  a  separate  science, 
p-ychology,  although  the  boundary  line  between  psychology  as  it  exists  at 
present  and  the  scientific  physiology  of  the  nervous  system  cannot  always  be 
sharply  drawn. 

It  follows  clearly  enough  from  what  has  been  said  of  the  methods  used  in 
animal  physiology  that  even  an  elementary  acquaintance  with  the  subject  as  a 
science  requires  some  knowledge  of  general  histology  and  anatomy,  human  as 
well  as  comparative,  of  physics,  and  of  chemistry.  When  this  preliminary 
training  is.  lacking,  physiology  cannot  be  taught  as  a  science;  it  becomes 
simply  a  heterogeneous  mass  of  facts,  and  fails  to  accomplish  its  function  as  a 
preparation  for  the  scientific  study  of  medicine.  The  mere  facts  of  physiology 
arc  valuable,  indeed  indispensable,  as  a  basis  for  the  study  of  the  succeed  im.: 
branches  of  the  medical  curriculum,  but  in  addition  the  subject,  properly 
taught,  should  impart  a  scientific  discipline  and  an  acquaintance  with  the 
possible  methods  of  experimental  medicine  ;  for  among  the  so-called  experi- 
mental branches  of  medicine  physiology  is  the  most  developed  and  the  ino.-t 
exact,  and  serves  as  a  type,  so  far  as  methods  are  concerned,  to  which  the 
others  must  conform. 


II.  BLOOD  AND  LYMPH. 


BLOOD. 

A.   General  Properties  :   Physiology  op  the  Corpuscles. 

The  blood  of  the  body  is  contained  in  a  practically  closed  system  of  tubes, 
the  blood-vessels,  within  which  it  is  kept  circulating  by  the  force  of  the  heart- 
beat. The  blood  is  usually  spoken  of  as  the  nutritive  liquid  of  the  body,  but 
its  functions  may  be  stated  more  explicitly,  although  still  in  quite  general 
terms,  by  saying  that  it  carries  to  the  tissues  food-stuffs  after  they  have  been 
properly  prepared  by  the  digestive  organs;  that  it  transports  to  the  tissues 
oxygen  absorbed  from  the  air  in  the  lungs ;  that  it  carries  off  from  the  tissues 
various  waste  products  formed  in  the  processes  of  disassimilatioD  ;  that  it  i> 
the  medium  for  the  transmission  of  the  internal  secretion  of  certain  glands  ; 
and  that  it  aids  in  equalizing  the  temperature  and  water  contents  of  the  body. 
It  is  quite  obvious,  from  these  statements,  that  a  complete  consideration  of 
the  physiological  relations  of  the  blood  would  involve  substantially  a  treat- 
ment of  the  whole  subject  of  physiology.  It  is  proposed,  therefore,  in  this 
section  to  treat  the  blood  in  a  restricted  way — to  consider  it,  in  fact,  as  a  tissue 
in  itself,  and  to  study  its  composition  and  properties  without  special  reference 
to  its  nutritive  relationship  to  other  parts  of  the  body. 

Histological  Structure. — The  blood  is  composed  of  a  liquid  part,  the 
plasma,  in  which  float  a  vast  number  of  microscopic  bodies,  the  blood-corpus- 
cles. There  are  at  least  three  different  kinds  of  corpuscles,  known  respectively 
as  the  red  corpuscles;  the  white  corpuscles  or  leucocytes,  of  which  in  turn 
there  are  a  number  of  different  kinds;  and  the  blood-plate*.  As  the  details 
of  structure,  size,  and  number  of  these  corpuscles  belong  properly  to  text- 
books on  histology,  they  will  be  mentioned  only  incidentally  in  this  section 
when  treating  of  the  physiological  properties  of  the  corpuscles.  Blood-plasma, 
when  obtained  free  from  corpuscles,  is  perfectly  colorless  in  thin  layers — for 
example,  in  microscopic  preparations;  when  seen  in  large  quantities  it  shows  a 
slightly  yellowish  tint,  the  depth  of  color  varying  with  dillerent  animals.  This 
color  is  due  to  the  presence  in  small  quantities  of  a  special  pigment,  the  nature 
of  which  is  not  definitely  known.  The  ml  color  of  blood  is  not  due,  there- 
fore, to  coloration  of  the  blood-plasma,  but  is  caused  by  the  mass  of  red  cor- 
puscles held  in  suspension  in  this  liquid.  The  proportion  by  bulk  of  plasma 
to  corpuscles  is  usually  given,  roughly,  as  two  to  one. 

Illood-xcrum  and  I  )<jlbrinafed  Blood. —  In  connection  with    the   explanation 

of  the  term  "  blood-plasma"  just  given,  it  will  be  convenient  to  define  briefly 

the  terms  "  blood-serum  "  and  "defibrinated  blood."     Blood,  after  it  escapes 

from   the   vessels,  usually  clots  or  coagulates;  the  nature  of  this  process  is 

Vol.  I.— 3  :v.\ 


34  AN    AMERICAN    TEXT- HOOK    OF    PHYSIOLOGY. 

discussed  in  detail  on  p.  54.  The  clot,  as  it  forms,  gradually  shrinks  and 
squeezes  out  a  clear  liquid  to  which  the  name  blood-serum  is  given.  Serum 
resembles  the  plasma  of  normal  blood  in  general  appearance,  but  differs  from 
it  in  composition,  as  will  be  explained  later.  At  present  we  may  say,  by  way 
<>f  a  preliminary  definition,  that  blood-serum  is  the  liquid  part  of  blood  after 
coagulation  has  taken  place,  as  blood-plasma  is  the  liquid  part  of  blood  before 
coagulation  has  taken  place.  If  shed  blood  is  whipped  vigorously  with  a  rod 
or  some  similar  object  while  it  is  clotting,  the  essential  part  of  the  clot — 
namely,  the  fibrin — forms  differently  from  what  it  docs  when  the  blood  i- 
allowed  to  coagulate  quietly;  it  is  deposited  in  shreds  on  the  whipper.  Blood 
thai  has  been  treated  in  this  way  is  known  as  defibrinated  blood.  It  consists 
of  blood-serum  plus  the  red  and  white  corpuscles,  and  as  far  as  appearance- 
go  it  resembles  exactly  normal  blood  ;  it  has  lost,  however,  the  power  of  clot- 
ting. A  more  complete  definition  of  these  terms  will  be  given  after  the  sub- 
ject of  coagulation  has  been  treated. 

Reaction. — The  reaction  of  blood  is  alkaline,  owing  mainly  to  the  alka- 
line salts,  especially  the  carbonates  of  soda,  dissolved  in  the  plasma.  The 
degree  of  alkalinity  varies  with  different  animals:  reckoned  as  Xa,C03,  the 
alkalinity  of  dog's  blood  corresponds  to  0.2  per  cent,  of  this  salt;  of  human 
blood,  0.35  per  cent.  The  alkaline  reaction  of  blood  is  very  easily  demon- 
sl  rated  upon  clear  plasma  free  from  corpuscles,  but  with  normal  blood  the  red 
color  prevents  the  direct  application  of  the  litmus  test.  \  number  of  simple 
devices  have  been  suggested  to  overcome  this  difficulty.  For  example,  the 
method  employed  by  Zuutz  is  to  soak  a  strip  of  litmus-paper  in  a  concentrated 
solution  of  NaCl,  to  place  on  this  paper  a  drop  of  blood,  and,  after  a  few 
seconds,  to  remove  the  drop  with  a  stream  of  water  or  with  a  piece  of  filter- 
paper.  The  alkaline  reaction  becomes  rapidly  less  marked  after  the  blood  has 
been  shed;  it  varies  also  slightly  under  different  conditions  of  normal  life 
and  in  certain  pathological  conditions.  After  meals,  for  instance,  during  the 
act  of  digestion,  it  is  said  to  be  increased,  while,  on  the  contrary,  exercise 
causes  a  diminution.  In  no  case,  however,  does  the  reaction  become  acid. 
For  details  of  the  methods  used  for  quantitative  determinations  of  the  alka- 
linitv  of  human  blood,  reference  must  be  made  to  original  sources.1 

Specific  Gravity. — The  specific  gravity  of  human  blood  in  the  adult  male 
may  vary  from  1041  to  1067,  the  average  being  about  1055.  Jones2  made 
a  careful  study  of  the  variations  in  specific  gravity  of  human  blood  under 
different  conditions  of  health  and  disease,  making  use  of  a  simple  method 
which  requires  only  a  few  drops  of  blood  for  each  determination.  He  found 
that  the  specific  gravity  varies  with  age  and  sex,  that  it  is  diminished  after 
eating  and  is  increased  by  exercise,  that  it  falls  slowly  during  the  day  and 
rises  gradually  during  the  night,  and  that  it  varies  greatly  in  individuals,  "so 
much  so  that  a  specific  gravity  which  is  normal  for  one  may  be  a  sign  of  dis- 
ease in  another."      The  specific  gravity  of  the  corpuscles  is  slightly  greater 

1  Wright:  The  Lancet,  1897,  p.  8;  Winternitz:  Zeitschrifl  furphysiol.  Chemie,  1891,  Bd.  15, 
s.  505. 

2  Journal  o)  PhysiiAofjy,  1891,  vol.  xii.,  p.  299. 


BLOOD.  35 

than  that  of  the  plasma.  For  this  reason  the  corpuscles  in  shed  blood,  when 
its  coagulation  is  prevented  or  retarded,  tend  to  settle  to  the  bottom  of  the 
containing  utensil,  leaving  a  more  or  less  clear  layer  of  supernatant  plasma. 
Among  themselves,  also,  the  corpuscles  differ  slightly  in  specific  gravity,  the 
red  corpuscles  being  heaviest  and  the  blood-plates  being  lightest. 

Red  Corpuscles. — The  red  corpuscles  in  man  and  in  all  the  mammalia, 
with  the  exception  of  the  camel  and  other  members  of  the  group  Camelidae, 
are  biconcave  circular  disks  without  nuclei;  in  the  Camelidae  they  have  an 
elliptical  form.  Their  average  diameter  in  man  is  given  as  7.7 ft  (1//  =  0.001 
of  a  mm.);  their  number,  which  is  usually  reckoned  as  so  many  in  a  cubic 
millimeter,  varies  greatly  under  different  conditions  of  health  and  disease. 
The  average  number  is  given  as  5,000,000  per  cubic  mm.  for  males  and 
4,500,000  for  females.  The  red  color  of  the  corpuscles  is  due  to  the  presence 
in  them  of  a  pigment  known  as  "  haemoglobin."  Owing  to  the  minute  size 
of  the  corpuscles,  their  color  when  seen  singly  under  the  microscope  is  a 
faint  yellowish-red,  but  when  seen  in  mass  they  exhibit  the  well-known 
blood-red  color,  which  varies  from  scarlet  in  arterial  blood  to  purplish-red 
in  venous  blood,  this  variation  in  color  being  dependent  upon  the  amount  of 
oxygen  contained  in  the  blood  in  combination  with  the  haemoglobin.  Speaking 
generally,  the  function  of  the  red  corpuscles  is  to  carry  oxygen  from  the  lungs 
to  the  tissues.  This  function  is  entirely  dependent  upon  the  presence  of 
haemoglobin,  which  has  the  power  of  combining  easily  with  oxygen  gas.  The 
physiology  of  the  red  corpuscles,  therefore,  is  largely  contained  in  a  description 
of  the  properties  of  haemoglobin. 

Condition  of  the  Haemoglobin  in  the  Corpuscle. — The  finer  structure 
of  the  red  corpuscle  is  not  completely  known.     It  is  commonly  believed  that 
the  corpuscle  consists  of  two  substances — a  delicate,  extensible,  colorless  pro- 
toplasmic material,  which  gives  to  the  corpuscle  its  shape  and  which  is  known 
as  the  stroma,  and  the  haemoglobin.    The  latter  constitutes  the  bulk  of  the  cor- 
puscle, forming  as  much  as  95  per  cent,  of  the  solid  matter.     It  was  formerly 
thought   that  haemoglobin  is  disseminated   as  such   in   the   interstices  of  the 
porous  spongy  stroma,  but  there  seem  to  be  reasons   now  for  believing  that 
it  is  present    in   the  corpuscles  in   some  combination  the  nature  of  which   is 
not  fully  known.     This  belief  is  based  upon  the  fact  that  Hoppe-Seyler '  has 
shown  that  haemoglobin  while  in  the  corpuscles  exhibits  certain  minor  differ- 
ences in  properties  as  compared  with  haemoglobin  outside  the  corpuscles.     In 
various  ways  the  compound  of  haemoglobin  in  the  corpuscles  may  be  destroyed, 
the  haemoglobin  being  set  iri'v  and  passing  into  solution  in  the  plasma.     Blood 
in  which  this  change  has  occurred  is  altered  in  color  and   is  known  as  "  laky 
blood."       In    thin    layers   it    is   transparent,    whereas   normal    blood    with    the 
haemoglobin  still  in  the  corpuscles  is  quite  opaque  even   in  very  thin  strata. 
Blood  may  be  made  laky  by  the  addition  of  ether,  of  chloroform,  of  bile  or 
the  bile  acids,  of  the  serum   of  other  animals,  by  an   excess  of  water,   by 
alternately   freezing  and   thawing,  and    by  a    number  of  other   methods.      In 
connection  with  two  of  these   methods  of  discharging   haemoglobin   from  the 
1  ZeUschrifi  fur  physiologische  Chemie,  Bd,  xiii.,  1889,  S.  177. 


3b'  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

corpuscles  there  have  come  into  use  in  current  medical  and  physiological 
literature  two  technical  terms  which   it   may  be  well  to  attempt  to  define. 

Globulicidal  Action  of  Serum. — It  was  shown  first  by  Landois  that  the 
serum  of  one  animal  may  have  the  property  of  destroying  the  red  corpuscles 
in  the  blood  of  another  animal,  thus  making  the  blood  laky.  This  fact,  which 
ha-  since  been  investigated  more  fully,  is  now  designated  under  the  term  of 
" globulicidal  "  action  of  the  serum.  Jt  has  been  found  that  different  kinds  of 
serum  show  different  degrees  of  globulicidal  activity,  and  that  white  as  well  as 
red  corpuscles  may  be  destroyed.  Dog's  serum  or  human  serum  is  strongly 
globulicidal  to  rabbit's  blood.  Tt  would  seem  that  this  action  is  not  due  to 
mere  variations  in  the  amounts  of  inorganic  salts  in  the  different  kinds  of 
serum,  since  the  remarkable  tact  has  been  discovered  that  heating  serum  to 
55°  or  60°  C.  for  a  few  minutes  destroys  its  globulicidal  action,  although  such 
treatment  causes  no  coagulation  of  the  proteids  nor  any  visible  change  in  the 
liquid.  Moreover,  it  is  known  that  foreign  scrum  injected  into  the  veins  of  a 
living  animal  may  exert  a  marked  toxic  effect  that  cannot  be  explained 
solely  by  its  globulicidal  action — for  instance,  7  to  14  c.c.  of  fresh  dog's  serum 
will  suffice  to  kill  a  rabbit — and  lastly,  serum  is  known  to  exert  a  similar 
destructive  effect  on  bacteria,  its  so-called  bactericidal  action.  These  three 
effects  of  serum,  globulicidal,  bactericidal  and  toxic,  seem  all  to  be  destroyed 
I >y  heating  to  50°-60°  C,  and  it  is  possible  that  they  arc  all  traceable  to  the 
existence  in  the  blood  of  some  proteid  substance,  an  alexine,  which  is  present 
in  -mall  quantity  and  is  different  for  each  species  of  animal,  the  material 
in  the  blood  of  one  species  being  more  or  less  globulicidal  and  toxic,  as  a  rule, 
to  the  tissues  of  another  species.1 

Tsoto i iii-  Solutions. — When  blood  or  defibrinated  blood  is  diluted  with 
water,  a  point  is  soon  reached  at  which  haemoglobin  begins  to  pass  out  of  the 
corpuscles  into  the  plasma  or  the  serum,  and  the  blood  begins  to  appear  laky. 
It  appears  that  the  liquid  surrounding  the  corpuscles  must  have  a  certain 
concentration  as  regards  salts  or  other  soluble  substances,  such  as  sugar,  in 
order  to  prevent  the  entrance  of  water  into  the  substance  of  the  corpuscle. 
Normally  the  substance  of  the  red  corpuscle  possesses  a  certain  osmotic 
pressure  which  may  be  supposed  to  be  equal  to  that  of  the  plasma  by  which 
it  is  surrounded,  so  that  the  interchange  of  water  between  them  is  at  an 
equilibrium.  If  the  concentration  of  the  outside  Liquid  is  diminished,  this 
equilibrium  is  destroyed  and  water  passes  into  the  corpuscle ;  if  the  dilution 
has  been  sufficient,  enough  water  passes  into  the  corpuscle  to  make  it  swell 
and  eventually  to  force  out  the  haemoglobin.  Liquids  containing  inorganic  salt-, 
or  other  soluble  substances  that  possess  an  osmotic  pressure  sufficient  to  pre- 
vent the  imbibition  of  water  by  the  corpuscles,  are  -aid  to  be  "isotonic  to  the 
corpuscles."  Red  corpuscles  suspended  in  such  liquids  do  not  change  in  shape 
nor  lose  their  haemoglobin.  When  solutions  of  different  substances  are  com- 
pared from  this  standpoint,  it  is  found  that  the  concentration  necessary  varies 
with  the  substance  used.  Tim-,  a  solution  ofNaClofO.64  per  cent,  is  isotonic 

1  For  :i  recenl  paper  .-mil  the  literature  see  Friedenthal  and   Lewandowsky,  Arehiv  fiir  Phys~ 
-    531. 


BLOOD.  37 

with  a  solution  of  sugar  of  5.5  per  cent,  or  a  solution  of  KX03  of  1.09  per 
cent.  When  placed  in  any  of  these  three  solutions  red  corpuscles  <1<»  not 
take  up  water — at  least  not  in  quantities  sufficient  to  discharge  the  haemo- 
globin. For  a  more  complete  account  of  these  relations  the  reader  is  referred 
to  original  sources  (Hamburger1).  A  solution  whose  osmotic  pressure  is 
lower  than  that  of  blood-plasma  is  said  to  be  hypo-isotonic  <>r  hypotonic  to 
blood.  Such  solutions  may  cause  the  blood  to  lake.  Solutions  of  a  higher 
osmotic  pressure  than  that  of  the  plasma  are  spoken  of  as  hvper-isotonic  or 
hypertonic.  Whenever  it  is  necessary  to  dilute  shed  blood  or  to  inject  any 
quantity  of  a  neutral  liquid  into  the  circulation  care  must  be  taken  to  have 
the  solution  isotonic  with  the  blood.  (See  p.  65  for  an  explanation  of  the 
term  osmotic  pressure.) 

Nature  and  Amount  of  Haemoglobin. — Haemoglobin  is  a  very  complex 
substance  belonging  to  the  group  of  combined  proteids.  (For  the  definition 
and  classification  of  proteids,  as  well  as  for  the  purely  chemical  properties  of 
haemoglobin  and  its  derivatives,  reference  must  be  made  to  the  section  on  "The 
Chemistry  of  the  Body.")  When  decomposed  in  various  ways  haemoglobin 
breaks  up  into  a  proteid  (globin,  86  to  96  per  cent.),  a  simpler  pigment  (haemal- 
tin,  4  per  cent.),  and  an  unknown  residue.2  When  the  decomposition  takes 
place  in  the  absence  of  oxygen,  the  products  formed  are  globin  and  haemo- 
chromogen,  instead  of  globin  and  luematin.  Haemochromogen  in  the  presence 
of  oxygen  quickly  undergoes  oxidation  to  the  more  stable  luematin.  Hoppe- 
Seyler  has  shown  that  haemochromogen  possesses  the  chemical  grouping  which 
gives  to  haemoglobin  its  power  of  combining  readily  with  oxygen  and  its 
distinctive  absorption  spectrum.  On  the  basis  of  facts  such  as  these,  haemo- 
globin may  be  defined  as  a  compound  of  a  proteid  body  with  haemochromogen. 
It  seems,  then,  that  although  the  haemochromogen  portion  is  the  essential 
tiling,  giving  to  the  molecule  of  haemoglobin  its  valuable  physiological  prop- 
erties as  a  respiratory  pigment,  yet  in  the  blood-corpuscles  this  substance  is 
incorporated  into  the  much  larger  and  more  unstable  molecule  of  haemoglobin, 
whose  behavior  toward  oxygen  is  different  from  that  of  the  haemochromogen 
itself,  the  difference  being  mainly  in  the  fact  that  the  haemoglobin  as  it  exists 
in  the  corpuscles  forms  with  oxygen  a  comparatively  feeble  combination  that 
may  be  broken  up  readily  with  liberation  of  the  gas. 

Haemoglobin  is  widely  distributed  throughout  the  animal  kingdom,  being 

found   in   the   blood-corpuscles  of  mammalia,   birds,  reptiles,  amphibia,  and 

fishes,  and   in   the;   blood   or   blood-corpuscles  of  many  of  the  invertebrates. 

The  compositi >f  its  molecule  is  found  to  vary  somewhat  in  different  animals, 

so  that,  strictly   speaking,   there   are   probably   a  number   of   different    (onus 

of  haemoglobin — all,  however,  closely  related    in   chemical    and    physiological 

properties.     Elementary  analysis  of  dog's   haemoglobin  shows  the  following 

percentage    composition    (Jaquet) :    C  53.91,   H   6.62,   N    15.98,  S   0.542, 

Fe  0.333,  O  22.62.     Its  molecular  formula   is  given  as  <  \J  I ,..,,, N,,,S,Fe<  ),ls, 

which  would  make  the  molecular  weight  16. <>(!!».    Other  estimates  are  given  of 

1  Du  Bois-Keyniond's  Arehivfur  Physiologic,  L886,  8.  176;  1887,  8.  31. 

1  See  Scbnlz,  Zeitschrift  fur  physiol.  Chemie,  Bd.  24;  also  Lauraw,  ibid.,  Bd.  26. 


38  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

the  molecular  formula,  but  they  agree  at  least  iu  showing  that  the  molecule 
is  of  enormous  size.  The  molecular  formula  for  haemochromogen  is  much  sim- 
pler; one  estimate  makes  it  C31H.j6X4Fe05.    The  exact  amount  of  heemoglobin 

in  human  blood  varies  naturally  with  the  individual  and  with  different  condi- 
tions of  life.  According  to  Preyer,1  the  average  amount  for  the  adult  male  is 
14  grams  of  haemoglobin  to  each  100  grams  of  blood.  It  is  estimated  that  in 
the  blood  of  a  man  weighing  68  kilos,  there  are  contained  about  750  grams  of 
haemoglobin,  which  is  distributed  among  some  twenty-five  trillions  of  corpuscles, 
giving  a  total  superficial  area  of  about  3200  square  meters.  Practically  all  of 
t  1 1 i  —  large  surface  of  haemoglobin  is  available  for  the  absorption  of  oxygen 
from  the  air  in  the  lungs,  for,  owing  to  the  great  number  and  the  minute 
size  of  the  capillaries,  the  blood,  in  passing  through  a  capillary  area,  becomes 
subdivided  to  such  an  extent  that  the  red  corpuscles  stream  through  the  capil- 
laries, one  may  say,  in  single  file.  In  circulating  through  the  lungs,  therefore, 
each  corpuscle  becomes  exposed  more  or  less  completely  to  the  action  of  the 
air,  and  the  utilization  of  the  entire  quantity  of  haemoglobin  must  be  nearly 
perfect.  It  may  be  worth  while  to  call  attention  to  the  fact  that  the  biconcave 
form  of  the  red  corpuscle  increases  the  superficies  of  the  corpuscle  and  tends 
to  make  the  surface  exposure  of  the  haemoglobin  more  complete. 

Compounds  with  Oxygen  and  other  Gases. — Haemoglobin  has  the 
property  of  uniting  with  oxygen  gas  in  certain  definite  proportions,  forming  a 
true  chemical  compound.  This  compound  is  known  as  oxyhoemoglobin  ; 
it  is  formed  whenever  blood  or  haemoglobin  solutions  are  exposed  to  air  or 
otherwise  brought  into  contact  with  oxygen.  Each  molecule  of  haemoglobin 
is  supposed  to  combine  with  one  molecule  of  oxygen,  and  it  is  usually  estimated 
that  1  gram  of  dried  haemoglobin  (dog)  can  take  up  1.59  c.c.  of  oxygen 
measured  at  0°  C.  and  TOO  mm.  of  barometric  pressure,  although  according 
to  a  later  determination  by  Hufneiy  the  ()-capacity  of  the  lib  of  ox's  blood 
is  only  1.34  c.c.  ()  to  each  gram  of  III).  Oxyhemoglobin  is  not  a  very  firm 
compound.  If  placed  iu  an  atmosphere  containing  no  oxvgen,  it  will  be 
dissociated,  giving  off  free  oxygen  and  leaving  behind  haemoglobin,  or,  :is 
it  is  often  called  by  way  of  distinction,  "reduced  haemoglobin."  This  power 
of  combining  with  oxygen  to  form  a  loose  chemical  compound,  which 
in  turn  can  be  dissociated  easily  wdien  the  oxygen-pressure  is  lowered, 
makes  possible  the  function  of  haemoglobin  in  the  blood  as  the  carrier 
of  oxygen  from  the  lungs  to  the  tissues.  The  details  of  this  process  are 
described  in  the  section  on  Respiration.  Haemoglobin  forms  with  carbon- 
monoxide  gas  (CO)  a  compound,  similar  to  oxyhemoglobin,  which  is 
known  as  carbon-monoxide  heemoglobin.  In  this  compound  also  the  union 
takes  place  in  tin'  proportion  of  one  molecule  of  haemoglobin  to  one 
molecule  of  the  gas.  The  compound  formed  differs,  however,  from  oxy- 
haemoglobin  in  being  much  more  stable,  and  it  is  for  this  reason  that  the 
breathing  of  carbon  monoxide  gas  is  liable  to  prove  fatal.  The  CO  unites 
with  the  haemoglobin,  forming  a  firm  compound;  the  tissues  of  the  bod v  are 

1  Die  Blutkrystalle,  Jena,  1871. 

2  Archir  Oh-  Physiologie,  1894,  8.  130. 


BLOOD.  39 

thereby  prevented  from  obtaining  their  necessary  oxygen,  and  death  results 
from  suffocation  or  asphyxia.  Carbon  monoxide  forms  one  of  the  constituents 
of  coal-gas.  The  well-known  fatal  effect  of  breathing  coal-gas  for  some  time, 
as  in  the  case  of  individuals  sleeping  in  a  room  where  gas  is  escaping,  is  trace- 
able directly  to  the  carbon  monoxide.  Nitric  oxide  (NO)  forms  also  with 
haemoglobin  a  definite  compound  that  is  even  more  stable  than  the  CO- 
haemoglobin ;  if,  therefore,  this  gas  were  brought  into  contact  with  the  blood, 
it  would  cause  death  in  the  same  way  as  the  CO. 

Oxyhemoglobin,  carbon-monoxide  haemoglobin,  and  nitric-oxide  haemoglo- 
bin are  similar  compounds.  Each  is  formed,  apparently,  by  a  definite  combina- 
tion of  the  gas  with  the  haemochromogen  portion  of  the  haemoglobin  molecule. 
and  a  given  weight  of  haemoglobin  unites  presumably  with  an  equal  volume  of 
each  gas.  In  marked  contrast  tothese  facts,  Bohr x  has  shown  that  haemoglobin 
forms  a  compound  with  carbon-dioxide  gas,  carbo-hcemoglobin,  in  which  the 
quantitative  relationship  of  the  gas  to  the  haemoglobin  differs  from  that  shown 
by  oxygen.  In  a  mixture  of  O  and  C02  each  gas  is  absorbed  by  haemoglobin 
solutions  independently  of  the  other,  so  that  a  solution  of  haemoglobin  nearly 
saturated  with  oxygen  can  unite  with  as  much  C02  as  though  it  held  no  oxygen 
in  combination.  Bohr  suggests,  therefore,  that  the  O  and  the  COL>  must  unite 
with  different  portions  of  the  haemoglobin — the  oxygen  with  the  pigment  portion, 
the  haemochromogen,  and  the  C02  possibly  with  the  proteid  portion.  It  seems 
probable  that  haemoglobin  plays  a  part  in  the  transportion  of  the  earl  ion 
dioxide  as  well  as  the  oxygen  of  the  blood,  but  its  exact  value  in  this  respect 
as  compared  with  the  blood-plasma,  which  also  acts  as  a  carrier  of  COa,  has 
not  been  definitely  determined  (see  Respiration). 

Presence  of  Iron  in  the  Molecule. — It  is  probable  that  iron  is  quite 
generally  present  in  the  animal  tissues  in  connection  with  nuclein  compounds, 
but  its  existence  in  haemoglobin  is  noteworthy  because  it  has  long  been  known 
and  because  the  important  property  of  combining  with  oxygen  seems  to  be 
connected  with  the  presence  of  this  element.  According  to  the  analyses 
made,  the  proportion  of  iron  in  haemoglobin  varies  somewhat  in  different 
animals:  the  figures  given  arc  from  0.335  to  0.47  per  cent.  The  amount  of 
haemoglobin  in  blood  may  he  determined,  therefore,  by  making  a  quantitative 
determination  of  the  iron.  The  amount  of  oxygen  with  which  haemoglobin 
will  combine  may  he  expressed  by  saying  that  one  molecule  of  oxygen  will 
be  fixed  for  each  atom  of  iron  in  the  haemoglobin  molecule.  In  the  decom- 
position of  haemoglobin  into  globulin  and  haematin,  which  has  been  spoken  of 
above,  the  iron  is  retained  in  the  haematin. 

Crystals. —  Haemoglobin  maybe  obtained  readily  in  the  form  of  crystals 
(Fig.  1).  As  usually  prepared,  these  crystals  are  really  oxyhaemoglobin,  but 
it  has  been  shown  that  reduced  haemoglobin  also  crystallizes,  although  with 
more  difficulty.  Haemoglobin  from  the  blood  of  different  animals  varies  to  a 
marked  degree  in  resped  to  the  power  of  crystallization.  From  the  blood  of 
the  rat,  do^,  cat,  guinea-pig,  and  horse,  crystals  arc  readily  obtained,  while 
haemoglobin  from  the  blood  of  man  and  of  most  of  the  vertebrates  crystallizes 

1  Skandivavisches  Archivf&r  Physiologie,  1892,  Bd.  '■'<.  S.  -17. 


40 


AN  AMERICAN    7 1: XT-BOOK    OF   PHYSIOLOGY. 


much  less  easily.  Methods  tor  preparing  and  purifying  these  crystals  will  be 
found  in  works  on  Physiological  Chemistry.  To  obtain  specimens  quickly 
for  examination  under  the  microscope,  one  of  the  most  certain  methods  is 
to  take  some  blood   from  one  of  the  animals  whose  haemoglobin  ervstallizes 

easily,  plaee  it  in  a  test-tube,  add  to  it  a  few- 
drops  of  ether,  shake  the  tube  thoroughly 
until  the  blood  becomes  laky — that  is, 
until  the  haemoglobin  is  discharged  into 
the  plasma — and  then  place  the  tube 
on  ice  until  the  crystals  are  deposited. 
Small   portions    of    the  crystalline   sedi- 

Cment  may  then   be    removed  to    a   glass 
I  slide     for    examination.       Haemoglobin 

from  different  animals  varies  not  only 
as  to  the  ease  with  which  it  crystal- 
lizes, but  in  some  cases  also  as  to  the 
form  that  the  crystals  take.  In  man 
and  in  most  of  the  mammalia  haemoglo- 
bin is  deposited  in  the  form  of  rhom- 
bic prisms;  in  the  guinea-pig  it  crys- 
tallizes in  tetrahedra  (d,  Fig.  1),  and 
in  the  squirrel  in  hexagonal  plates.  The 
crystals  are  readily  soluble  in  water,  and 
by  repeated  crystallizations  the  haemo- 
globin may  be  obtained  perfectly  pure. 

Fig.  1. -Crystallized hemoglobin  fafter  Frey):      ^s    j„    tne   case  of  Other  Soluble    proteid- 
a,  b,  crystals  from  venous  blood  of  man  ;  r,  from       t  .  , 

the  blood  of  a  cat;  d,  from  the  blood  of  a    like  bodies,  solutions  of  haemoglobin  are 

gninea-pig;  .from  the  blood  of  a  hamster;  /,  precipitated  by  alcohol,  by  mineral  acids, 
from  the  blood  of  a  squirrel.  l  L  J  »     J 

by  salts  of  the  heavy  metals,  by  boiling, 

etc.  Notwithstanding  the  fact  that  haemoglobin  crystallizes  so  readily,  it  is  not 
easily  dialyzable,  behaving  in  this  respect  like  proteids  and  other  colloidal 
bodies.  The  compounds  which  haemoglobin  forms  with  carbon  monoxide 
(CO)  and  nitric  oxide  (XO)  are  also  crystallizable,  the  crystals  being  isomor- 
phous  with  those  of  oxyhemoglobin. 

Absorption  Spectra. — Solutions  of  haemoglobin  and  its  derivative  com- 
pounds, when  examined  with  a  spectroscope,  give  distinctive  absorption  bands. 
A  brief  account  of  the  principle  and  arrangement  of  the  spectroscope,  although 
1 1 n necessary  for  those  familiar  with  the  elements  of  Physics,  is  given  by  way 
of  introduction  to  the  description  of  these  absorption  bands. 

Light,  when  made  to  pass  through  a  glass  prism,  is  broken  up  into  its  constituent 
rays,  giving  the  play  of  rainbow  colors  known  as  the  spectrum.  A  spectroscope  is 
an  apparatus  for  producing  and  observing  a  spectrum.  A  simple  form,  which  illus- 
trates sufficiently  well  the  construction  of  the  apparatus,  is  shown  in  Figure  2,  P 
being  the  glass  prism  giving  the  spectrum.  Light  falls  upon  this  prism  through 
the  tube  (a)  to  the  left,  known  as  the  "collimator  tube."  A  slit  at  the  end  of  this 
tube  (s)  admits  a  narrow  slice  of  light — lamplight  or  sunlight — which  then,  by 
means  of  a  convex  lens  at  the  other  end  of  the  tube,  is  made  to  fall  upon  the  prism 


BLOOD. 


41 


(p)  with  its  rays  parallel.  In  passing  through  the  prism  the  rays  are  dispersed  by 
unequal  refraction,  giving  a  spectrum.  The  spectrum  thus  produced  is  examined  by 
the  observer  with  the  aid  of  the  telescope  (b).  When  the  telescope  is  properly  focussed 
for  the  rays  entering  it  from  the  prism  (p),  a  clear  picture  of  the  spectrum  is  seen.  The 
length  of  the  spectrum  will  depend  upon  the  nature  and  the  number  of  prisms  through 
which  the  light  is  made  to  pass.  For  ordinary  purposes  a  short  spectrum  is  preferable 
for  hemoglobin  bands,  and  a  spectroscope  with  one  prism  is  generally  used.  If  the 
source  of  light  is  a  lamp-flame  of  some  kind,  the  spectrum  is  continuous,  the  colors 
gradually  merging  one  into  another  from  red  to  violet.  If  sunlight  is  used,  the  spectrum 
will  be  crossed  by  a  number  of  narrow  dark  lines  known  as  the  "  Frauuhofer  lines" 


pIG  o  —  Spectroscope :  p,  the  glass  prism  ;  a,  the  collimator  tube,  showing  the  slit  (s)  through  which  the 
light  is  admitted  ;  b,  the  telescope  for  observing  the  spectrum. 

(see  PL  I. ,  Frontispiece,  for  an  illustration  in  colors  of  the  solar  spectrum).  The  position  of 
these  lines  in  the  solar  spectrum  is  fixed,  and  the  more  distinct  ones  are  designated  by  letters 
of  the  alphabet,  A,  b,  c,  d,  e,  etc.,  as  shown  in  the  charts  below.  If  while  using  solar 
light  or  an  artificial  light  a  solution  of  any  substance  which  gives  absorption  bands  is 
so  placed  in  front  of  the  slit  that  the  light  is  obliged  to  traverse  it,  the  spectrum  as 
observed  through  the  telescope  will  show  one  or  more  narrow  or  broad  black  bands, 
that  are  characteristic  of  the  substance  used  and  constitute  its  absorption  spectrum.  The 
positions  of  these  bands  may  be  designated  by  describing  their  relations  to  the  Frauu- 
hofer lines,  or  more  directly  by  stating  the  wave-lengths  of  the  portions  of  the  spectrum 
between  which  absorption  takes  place.  Some  spectroscopes  are  provided  with  a  scale 
of  wave-lengths  superposed  on  the  spectrum,  and  when  properly  adjusted  this  scale 
enables  one  to  read  off  directly  the  wave-lengths  of  any  part  of  the  spectrum. 

When  very  dilute  solutions  of  oxyhemoglobin  are  examined  with  the 
spectroscope,  two  absorption  hands  appear,  both  occurring  in  the  portion  of 
the  spectrum  included  between  the  Frauuhofer  lines  i>  and  E.  The  band 
nearer  the  red  end  of  the  spectrum  is  known  as  the  "a-band  ;"  it  is  narrower, 
darker,  and  more  clearly  defined  than  the  other,  the  "/3-band  "  (Ki^-.  3,  and 
also  PI.  I.  spectrum  4).  With  a  solution  containing  0.0!'  per  cent,  of  oxy- 
hemoglobin, and  examined  in  layers  one  centimeter  thick,  the  a-band  extends 
over  the    part  of  the   spectrum    included    between   the    wave-lengths  I  oS.'i 


42 


AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 


(583  millionths  of  a  millimeter)  and  /  571,  and  the  ,9-band  between  X  550  and 
/  532  (Gamgee).  The  width  and  distinctness  of  the  bands  vary  naturally 
with  the  concentration  of  the  solution  used  (see  PI.  I.  spectra  2,  .'>,  4,  and  5), 


70      65 


55 


B    C 





It 


E    b 


F 


G 


Fig.  3.— Diagrammatic  representation  of  the  absorption  spectrum  of  oxyhemoglobin  (after  Rollett). 
The  numerals  give  the  wave-lengths  in  hundred-thousandths  of  a  millimeter;  the  letters  Bhow  the 
positions  of  the  more  prominent  Fraunhofer  lines  of  the  solar  spectrum.  The  red  end  of  the  spectrum 
is  to  the  left.    The  a-band  is  to  the  right  of  d,  the  /3-band  to  the  left  of  e. 

or,  if  the  concentration  remains  the  same,  with  the  width  of  the  stratum  of 
liquid  through  which  the  light  passes.     With  a  certain  minimal  percentage  of 

oxyhemoglobin  (less  than  0.01  per 
cent.)  the  /3-band  is  lost  and  the  a- 
band  is  very  faint  in  layers  one  cen- 
timeter thick.  With  stronger  solu- 
tions the  bands  become  darker  and 
wider  and  finally  fuse,  while  some 
of  the  extreme  red  end  and  a  great 
deal  of  the  violet  end  of  the  spec- 
trum is  also  absorbed.  The  varia- 
tions in  theabsorption  spectrum  with 
differences  in  concentration  are  clear- 
ly shown  in  the  accompanying  illus- 
tration from  Rollett1  (Fig.  4) ;  the 
thickness  of  the  layer  of  liquid  is 
supposed  to  be  one  centimeter.  The 
numbers  on  the  right  indicate  the 
percentage  strength  of  the  oxy- 
hemoglobin solutions.  It  \vill  be 
noticed  that  the  absorption  which 
takes  place  as  the  concentration  of 
the  solution  increases  affects  the  fed- 
orange  end  of  the  spectrum  last  of  all. 
Solutions  of  reduced  haemo- 
globin examined  with  the  spectro- 
scope  show  only  one  absorption 
band,  known  sometimes  as  the 
"y-band."  This  band  lies  also  in 
the  portion  of  the  spectrum  included 
between  the  lines  i>  and  K;  its  relations  to  these  lines  and  the  bands  of 
oxyhemoglobin  are  shown  in  Figure  5  and  in  PI.  I.  spectrum  6.  The 
1  Hermann's  Handbuchder  Pkysiologie,  Bd.  iv.,  1880. 


Fig.  4. — Diagram  to  show  the  variations  in  the  ab- 
sorption spectrum  of  oxyhemoglobin  with  varying 
concentrations  of  the  solution  (after  Rollett).  The 
numbers  to  the  right  give  the  strength  "f  the  oxy- 
globin  solution  in  percentages;  the  lettersgive 
th<>  positions  of  the  Fraunhofer  lines.  To  ascertain 
tin-  amounl  of  absorption  for  any  given  concentration 
up  to  l  per  cent.,  draw  a  horizontal  line  across  tin' 
diagram  at  the  level  corresponding  to  the  concentra- 
tion. Where  this  line  passes  through  the  shaded  part 
of  the  diagram  absorption  takes  place,  and  the  width 
of  the  absorption  bands  i-  seen  al  once.  The  diagram 
.-how-  clearly  that  the  amount  of  absorption  increases 

a-  the  solutions  become  m<>rc ncentrated,  especially 

the  absorption  of  the  blue  end  of  the  spectrum.  It 
will  he  noticed  that  with  concentrations  between  or, 
and  0.7  per  cent,  the  two  bands  between  Dandi  fuse 
into  ' 


BLOOD. 


IS 


y-band  is  much  more  diffuse  than  the  oxyhemoglobin  bands,  and  its  limits 
therefore,  especially  in  weak  solutions,  are  not  well  defined;  in  solutions 
of  blood  diluted  100  times  with  water,  which  would  give  a  haemoglobin 
solution  of  about  0.14  per  cent.,  the  absorption  band  lies  in  the  part  of  the 
spectrum  included  between  the  wave-lengths  X  572  and  X  542.     The  width 


70      65 


B   C 


E    b 


Fig.  5.— Diagrammatic  representation  of  the  absorption  spectrum  of  haemoglobin  (reduced  haemoglo- 
bin) (after  Rollett).  The  numerals  give  the  wave-lengths  in  hundred-thousandths  of  a  millimeter  ;  the 
letters  show  the  positions  of  the  more  prominent  Fraunhofer  lines  of  the  solar  spectrum.  The  red  end 
of  the  spectrum  is  to  the  left.    The  single  diffuse  absorption  band  lies  between  d  and  e. 

and  distinctness  of  this  band  vary  also  with  the  concentration  of  the 
solution.  This  variation  is  sufficiently  well  shown  in  the  accompanying 
illustration  (Fig.  6),  which  is  a  companion  figure  to  the  one  just  given 
for  oxyhemoglobin  (Fig.  4).  It  will  be  noticed  that  the  last  light  to 
be  absorbed  in  this  case  is  partly  in  the  red  end  and  partly  in  the  blue, 
thus  explaining  the  purplish  color 
of  hemoglobin  solutions  and  of 
venous  blood.  Oxyhemoglobin  so- 
lutions can  be  converted  to  hemo- 
globin solutions,  with  a  correspond- 
ing change  in  the  spectrum  bands, 
by  placing  the  former  in  a  vacuum 
or,  more  conveniently,  by  adding 
reducing  solutions.  The  solutions 
most  commonly  used  for  this  pur- 
pose are  ammonium  sulphide  and 
Stokes's  reagent.1  If  a  solution  of 
reduced  hemoglobin  is  shaken  with 
air,  it  quickly  changes  to  oxyhemo- 
globin and  gives  two  bands  instead 
of  one  when  examined  through  the 
spectroscope.  Any  given  solution 
may  be  changed  in  this  way  from 
oxyhemoglobin  to  hemoglobin, 
and  the  reverse,  a  great  number 
of  times,  thus  demonstrating  the 
facility  with  which  haemoglobin 
takes  up  and  surrenders  oxygen. 

1  Stokes's  reagent  is  an  ammoniacal  solution  of  a  ferrous  salt.  It  is  made  by  dissolving  2 
parts  i  by  weighl )  of  ferrous  sulphate,  adding  .">  parts  of  tartaric  acid,  and  then  ammonia  to  dis- 
tinct  alkaline  reaction.     A  permanent  precipitate  should  not  be  obtained. 


Fig.  (i.— Diagram  to  show  the  variations  In  the  ab- 
sorption spectrum  of  reduced  haemoglobin  with  vary- 
ing concentrations  of  the  solution  (after  Rollett).  The 
numbers  to  the  right  give  the  strength  <>t'  the  haemo- 
globin solution  in  percentages ;  the  Letters  give  the  posi- 
tions of  the  Fraunhofer  Lines.  For  further  directions 
as  in  the  use  of  the  diagram,  see  the  description  of 
Figure  1. 


44  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

Solutions  of  carbon-monoxide  haemoglobin  also  give  a  spectrum  with  two 
absorption  bands  closely  resembling  in  position  and  appearance  those  of  oxy- 
hemoglobin (see  PI.  I.  spectrum  7).  They  are  distinguished  from  the  oxy- 
hemoglobin bands  by  being  slightly  nearer  the  blue  end  of  the  spectrum,  as 
may  be  demonstrated  by  observing  the  wave-lengths  or,  more  conveniently, 
by  superposing  the  two  spectra.  Moreover,  solutions  of  carbon-monoxide 
haemoglobin  are  not  reduced  to  haemoglobin  by  adding  Stokes's  liquid,  two 
bands  being  still  seen  after  such  treatment.  A  solution  of  carbon-monoxide 
haemoglobin  suitable  for  spectroscopic  examination  may  be  prepared  easily  by 
passing  ordinary  coal-gas  through  a  dilute  oxyhemoglobin  solution  for  a  few 
minutes  and  then  filtering. 

Derivative  Compounds  of  Haemoglobin. — A  number  of  compounds 
directly  related  to  haemoglobin  have  been  described,  some  of  them  being 
found  normally  in  the  body.  Brief  mention  is  made  of  the  best  known  of 
these  substances,  but  for  the  details  of  their  preparation  and  chemical  proper- 
ties reference  must  be  made  to  the  section  on  "  The  Chemistry  of  the  Body." 

Methcemoglobin  is  a  compound  obtained  by  the  action  of  oxidizing  agents 
on  haemoglobin  ;  it  is  frequently  found,  therefore,  in  blood  stains  or  patho- 
logical liquids  containing  blood  that  have  been  exposed  to  the  air  for  some 
time.  It  is  now  supposed  to  be  identical  in  composition  with  oxyhemoglobin, 
with  the  exception  that  the  oxygen  is  held  in  more  stable  combination. 
Methemoglobin  crystallizes  in  the  same  form  as  oxyhemoglobin,  and  has  a 
characteristic  spectrum  (PI.  I.  spectrum  8). 

//"  mochromogen  is  the  substance  obtained  when  haemoglobin  is  decomposed 
by  acids  or  by  alkalies  in  the  absence  of  oxygen.  It  crystallizes  and  has  a 
characteristic  spectrum. 

Hit  matin  (C32H30N4FeO3)  is  obtained  when  oxyhemoglobin  is  decomposed 
by  acids  or  by  alkalies  in  the  presence  of  oxygen.  It  is  amorphous  and  has  a 
characteristic  spectrum  (PI.  I.  spectra  9  and  10). 

lln mill  ((\32II;,„X1Fe03HCl)  is  a  compound  of  haematin  and  HC1,  and  is 
readily  obtained  in  crystalline  form.  It  is  much  used  in  the  detection  of 
blood  in  medico-legal  cases,  as  the  crystals  are  very  characteristic  and  are  easily 
obtained  from  blood-clots  or  blood-stains,  no  matter  how  old  these  may  be. 

Hcematoporphyrin  (C16HI8N203)  is  a  compound  characterized  by  the  absence 
of  iron.  It  is  frequently  spoken  of  as  "iron-free  haematin."  It  is  obtained 
by  the  action  of  strong  sulphuric  acid  on  haematin. 

Hcematoidin  (C16H18N203)  is  the  name  given  to  a  crystalline  substance 
found  in  old  blood-clots,  and  formed  undoubtedly  from  the  haemoglobin  of 
the  clotted  blood.  It  has  been  shown  to  be  identical  with  one  of  the  bile- 
pigments,  bilirubin.  Its  occurrence  is  interesting  in  that  it  demonstrates  the 
relationship  between  haemoglobin  and  the  bile-pigments. 

Histohcematins  are  a  group  of  pigments  .-aid  to  be  present  in  many  of  the 
tissues — for  example,  the  muscles.  They  are  supposed  to  be  respiratory  pig- 
ment-, and  are  related  physiologically,  and  possibly  chemically,  to  hemoglobin. 
They  have  not  been  isolated,  but  their  spectra  have  been  described. 


BLOOD.  45 

] HI c-pigments    and    Urinary  Pigments — Haemoglobin    is   regarded    as   the 
parent-substance  of  the  bile-pigments  and  the  urinary  pigments. 

Origin  and  Fate  of  the  Red  Corpuscles. — The  mammalian  red  corpuscle 
is  a  cell  that  has  lost  its  nucleus.  It  is  not  probable,  therefore,  that  any  given 
corpuscle  lives  for  a  great  while  in  the  circulation.  This  is  made  more  certain 
by  the  fact  that  hemoglobin  is  the  mother-substance  from  which  the  bile- 
pigments  are  made,  and,  as  these  pigments  are  being  excreted  continually,  it  is 
fair  to  suppose  that  red  corpuscles  are  as  steadily  undergoing  disintegration  in 
the  blood-stream.  Just  how  long  the  average  life  of  the  corpuscles  is  has  not 
been  determined,  nor  is  it  certain  where  and  how  they  go  to  pieces.  It  has 
been  suggested  that  their  destruction  takes  place  in  the  spleen,  but  the  observa- 
tions advanced  in  support  of  this  hypothesis  are  not  very  numerous  or  con- 
clusive. Among  the  reasons  given  for  assuming  that  the  spleen  is  especially 
concerned  in  the  destruction  of  red  corpuscles,  the  most  weighty  is  the  histo- 
logical fact  that  one  can  sometimes  find  in  teased  preparations  of  spleen-tissue 
certain  large  cells  which  contain  red  corpuscles  in  their  cell-substance  in  various 
stages  of  disintegration.  It  has  been  supposed  that  the  large  cells  actually 
ingest  the  red  corpuscles,  selecting  those,  presumably,  that  are  in  a  state  of 
physiological  decline.  Against  this  idea  a  number  of  objections  may  be 
raised.  Large  leucocytes  with  red  corpuscles  in  their  interior  are  not  found 
so  frequently  nor  so  constantly  in  the  spleen  as  we  would  expect  should  be 
the  case  if  the  act  of  ingestion  were  constantly  going  on.  There  is  some 
reason  for  believing,  indeed,  that  the  whole  act  of  ingestion  may  be  a  post- 
mortem phenomenon  ;  that  is,  after  the  cessation  of  the  blood-stream  the 
amoeboid  movements  of  the  large  leucocytes  continue,  while  the  red  corpuscles 
lie  at  rest — conditions  that  are  favorable  to  the  act  of  ingestion.  It  may  be 
added  also  that  the  blood  of  the  splenic  vein  contains  no  haemoglobin  in  solu- 
tion, indicating  that  no  considerable  dissolution  of  red  corpuscles  is  taking 
place  in  the  spleen.  Moreover,  complete  extirpation  of  the  spleen  does  not 
seem  to  lessen  materially  the  normal  destruction  of  red  corpuscles,  if  we  may 
measure  the  extent  of  that  normal  destruction  by  the  quantity  of  bile-pigment 
formed  in  the  liver,  remembering  that  haemoglobin  is  the  mother-substance 
from  which  the  bile-pigments  are  derived.  It  is  more  probable  that  there  is 
no  special  organ  or  tissue  charged  with  the  function  of  destroying  red  corpus- 
cles, and  that  they  undergo  disintegration  and  dissolution  while  in  the  blood- 
stream and  in  anv  part  of  the  circulation,  the  liberated  haemoglobin  being 
carried  to  the  liver  and  excreted  in  part  as  bile-pigment.  The  continual 
destruction  of  red  corpuscles  implies,  of  course,  a  continual  formation  of  new- 
ones.  It  has  been  shown  satisfactorily  that  in  the  adult  the  organ  for  the 
reproduction  of  red  corpuscles  is  the  red  marrow  of  bones.  In  this  tissue 
/in  inatopoiesis,  as  the  process  of  formation  of  red  corpuscles  is  termed,  goes  on 
continually,  the  process  being  much  increased  after  hemorrhages  and  in  certain 
pathological  conditions.  The  details  of  the  histological  changes  will  be  found 
in  the  text-books  of  histology.  It  is  sufficient  here  to  state  simply  that  a 
group  of  nucleated  colorless  cells,  erythroblasts,  i>  found  in  the  red  marrow. 


46  AN    AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

These  cells  multiply  by  karyokinesis,  and  the  daughter-cells  eventually  pro- 
duce haemoglobin  in  their  cytoplasm,  thus  forming  nucleated  red  corpuscles. 
The  nuclei  arc  subsequently  lost,  either  by  disintegration  or,  more  likely,  by 
extrusion,  and  the  newly-formed  non-nucleated  red  corpuscles  are  forced  into 
the  blood-stream,  owing  to  a  gradual  change  in  their  position  during  develop- 
ment caused  by  the  growing  haematopoietic  tissue.  When  the  process  has 
been  greatly  accelerated,  as  after  severe  hemorrhages  or  in  certain  pathological 
conditions,  red  corpuscles  still  retaining  their  nuclei  may  be  found  in  the  circu- 
lating blood,  having  been  forced  out  prematurely  as  it  were.  Such  corpuscles 
may  subsequently  lose  their  nuclei  while  in  the  blood-stream.  In  the  em- 
bryo, haematopoietic  tissue  is  found  in  parts  of  the  body  other  than  the  mar- 
row, notably  in  the  liver  and  spleen,  which  at  that  time  serve  as  organs  for 
the  production  of  new  red  corpuscles.  In  the  blood  of  the  young  embryo 
nucleated  red  corpuscles  are  at  first  abundant,  but  they  become  less  numerous 
as  the  fetus  grows  older.1 

Variations  in  the  Number  of  Red.  Corpuscles. — The  average  number 
of  red  corpuscles  for  the  adult  male,  as  has  been  stated  already,  is  usually 
given  as  5,000,000  per  cubic  mm.  The  number  is  found  to  vary  greatly, 
however.  Outside  of  pathological  conditions,  in  which  the  diminution  in 
number  may  be  extreme,  differences  have  been  observed  in  human  beings 
under  such  conditions  as  the  following:  The  number  is  less  in  females 
(4,500,000);  it  varies  in  individuals  with  the  constitution,  nutrition,  and 
manner  of  life;  it  varies  with  age,  being  greatest  in  the  fetus  and  in  the  new- 
born child  ;  it  varies  with  the  time  of  the  day,  showing  a  distinct  diminution 
after  meals;  in  the  female  it  varies  somewhat  in  menstruation  and  in  preg- 
nancv,  being  slightly  increased  in  the  former  and  diminished  in  the  latter 
condition.  Perhaps  the  most  interesting  example  of  variation  in  the  number 
of  red  corpuscles  is  that  which  occurs  with  changes  in  altitude.  Residence  in 
high  altitudes  is  quickly  followed  by  a  marked  increase  in  the  number  of  red 
corpuscles.  Viault 2  has  shown  that  living  in  the  mountains  for  two  weeks  at 
an  altitude  of  4.°>!)2  meters  caused  an  increase  in  the  corpuscles  from  5,000,000 
to  over  7,000,000  per  cubic  mm.,  and  in  the  third  week  the  number  reached 
8,000,000.  The  accuracy  of  this  observation  has  been  demonstrated  since  by 
many  investigators.  Some  very  careful  work  done  under  the  direction  of 
Miescher3  has  shown  that  a  comparatively  small  increase  in  altitude,  700 
meters,  causes  a  marked  increase  in  the  number  of  red  corpuscles  and  in  the 
amount  of  haemoglobin,  while  return  to  a  lower  altitude  quickly  brings  the 
blood  back  to  its  normal  condition.  From  these  observations  it  would  seem 
that  a  diminished  pressure  of  oxygen  in  the  atmosphere  stimulates  the  hema- 
topoietic organs  to  greater  activity,  and  it  is  interesting  to  compare  this  result 
with  the  effect  of  an  actual  loss  of  blood.  In  the  latter  case  the  production  of 
red  corpuscles  in  the  red  marrow  is  increased,  because,  apparently,  the  anaemic 
condition  causes  a  diminution  in  the  oxygen-supply  to  the  haematopoietic  tissue, 

1  Howell  :  "Life  History  of  the  Blood-corpuscles,"  etc.,  Journal  of  Morphology,  1890,  vol.  iv. 

2  La  s,  maine  m&dicale,  1890,  p.  4G4. 

s  Archiv  fib-  erp.  Pathol,  u.  Pharmakol.,  1897,  Bd.  39,  S.  426-464. 


BLOOD.  47 

and  thereby  stimulates  the  erythroblastic  cells  to  more  rapid  multiplication. 
Iu  the  case  of  a  diminution  in  oxygen-pressure,  as  happens  when  the  altitude 
is  markedly  increased,  we  may  suppose  that  one  result  is  again  a  slight  dimi- 
nution in  the  oxygen-supply  to  the  tissues,  including  the  red  marrow,  and  in 
consequence  the  erythroblasts  are  again  stimulated  to  greater  activity.  This 
variation  in  haemoglobin  with  the  altitude  is  an  interesting  adaptation  which 
ensures  always  a  normal  oxygen-capacity  for  the  blood. 

Physiolog-y  of  the  Blood-leucocytes. — The  function  of  the  blood-leuco- 
cytes has  been  the  subject  of  numerous  investigations,  particularly  in  connection 
with  the  pathology  of  blood  diseases.  Although  many  hypotheses  have  been 
made  as  the  result  of  this  work,  it  cannot  be  said  that  we  possess  any  positive 
information  as  to  the  normal  function  of  these  cells  in  the  body.  It  must  be 
borne  in  mind  in  the  first  place  that  the  blood-leucocytes  are  not  all  the  same 
histologically,  and  it  may  be  that  their  functions  are  as  diverse  as  is  their  mor- 
phology. Various  classifications  have  been  made,  based  upon  one  or  another 
difference  in  microscopic  structure  and  reaction.    Thus,  Ehrlich  groups  the  leuco- 


b 


Fig.  7.— Blood  stained  with  Ehrlich's  "triple  stain"  of  acid-fuchsin,  methyl-green,  and  orange  G. 
(drawn  with  the  camera  lucida  from  normal  blood)  (after  Osier):  a,  red  corpuscles;  b,  lymphocytes;  c, 
large  mononuclear  leucocytes;  <l,  transitional  forms;  >,  neutrophilic  leucocytes  with  polymorphous 
nuclei  (polynuclear  neutrophiles) ;  /,  eosinophilic  leucocytes. 

cytes  according  to  the  size,  the  solubility,  and  the  staining  of  the  granules 
(contained  in  the  cytoplasm,  making  in  the  latter  respect  three  main  groups; 
oxyphiles  or  eo&inophiles,  those  whose  granules  stain  only  with  acid  aniline 
dyes — that  is,  with  dyes  in  which  the  acid  part  of  the  dye  acts  as  the  stain  ; 
basophiles,  those  which  stain  only  with  basic-  dyes;  and  neutrophiles,  those 
which  stain  only  with  neutral  dyes1  (Fig.  7).  This  classification  is  fre- 
quently used,  especially  in  pathological  literature,  but  it  is  not  altogether 
satisfactory,  since  no  definite  functional  relationship  of  the  granules  has  been 
established  ;  and,  moreover,  it  is  undecided  whether  or  not  the  granules  arc 
permanent  or  temporary  structures   in   the  cells.      A    simpler   classification 

1  Ehrlich  :    Die  Ancemie,  Vienna,  1S98;  Kanthack   and   Hardy,  Journal  of  Physiology,  vol., 
xvii.,  1894,  p.  81. 


48  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

based  on  morphological  characteristics  is  the  following:  1.  Lymphocytes, 
which  arc  small  corpuscles  with  a  round  vesicular  nucleus  and  very  scanty 
cytoplasm  ;  they  are  not  capable  of  amoeboid  movements.  These  corpuscles 
are  so  called  because  they  resemble  the  leucocytes  found  in  the  lymph-glands, 
and  are  supposed  in  fact  to  be  brought  into  the  blood  through  the  lymph. 
According  to  Ehrlich,  they  form  from  22  to  25  per  cent,  of  the  total  number 
of  leucocytes.  2.  Mononuclear  leucocytes,  which  are  large  corpuscles  with  a 
vesicular  nucleus  and  abundant  cytoplasm  :  they  have  the  power  of  making 
amoeboid  movements  and  arc  present  in  only  small  numbers,  1  per  cent. 
3.  Polymorphous  or  polynucleated  leucocytes,  which  are  large  corpuscles  with 
the  nucleus  divided  into  lobes  that  are  either  entirely  separated  or  are  con- 
nected by  line  protoplasmic  threads.  This  form  shows  active  amoeboid  move- 
ments and  constitutes  the  largest  proportion  of  the  blood  leucocytes,  70  to  72 
per  cent.  4.  The  eosinophile  cells,  similar  in  general  to  the  last,  except  that 
the  cytoplasm  contains  numerous  coarse  granules  that  take  acid  stains  (eosin) 
readily.     They  are  present  in  small  numbers,  2  to  4  per  cent. 

It  is  impossible  to  say  whether  these  varieties  of  blood-leucocytes  are 
distinct  histological  units  that  have  independent  origins  and  more  or  less 
dissimilar  functions,  or  whether,  as  seems  more  probable  to  the  writer,  they 
represent  different  stages  in  the  development  of  a  single  type  of  cell,  the 
lymphocytes  forming  the  youngest  and  the  polymorphic  or  polynucleated 
leucocytes  the  oldest  stage.  Perhaps  the  most  striking  property  of  the  leuco- 
cytes as  a  class  is  their  powrer  of  making  amoeboid  movements — a  charac- 
teristic which  has  gained  for  them  the  sobriquet  of  "  wandering  "  cells.  By 
virtue  of  this  property  some  of  them  are  able  to  migrate  through  the  walls 
of  blood-capillaries  into  the  surrounding  tissues.  This  process  of  migration 
takes  place  normally,  but  is  vastly  accelerated  under  pathological  conditions. 
As  to  the  function  or  functions  fulfilled  by  the  leucocytes,  numerous  sugges- 
tions have  been  made,  some  of  which  may  be  stated  in  brief  form  as  follows: 
(1)  They  protect  the  body  from  pathogenic  bacteria.  In  explanation  of  this 
action  it  has  been  suggested  that  they  may  either  ingest  the  bacteria,  and  thus 
destroy  them  directly,  or  they  may  form  certain  substances,  defensive  proteids, 
that  destroy  the  bacteria.  Leucocytes  that  act  by  ingesting  the  bacteria 
are  spoken  of  as  "phagocytes"  {ipaystv,  to  eat;  xvrot;,  cell).  This  theory  of 
their  function  is  usually  designated  as  the  "phagocytosis  theory  of  Metschni- 
kotf ;"  it  is  founded  upon  the  fact  that  the  amoeboid  leucocytes  are  known  to 
ingest  foreign  particles  with  which  they  come  in  contact.  The  theory  of  the 
protective  action  of  leucocytes  has  been  used  largely  in  pathology  to  explain 
immunity  from  infectious  diseases,  and  for  details  of  experiments  in  support 
of  it  reference  must  be  made  to  pathological  text-books.  (2)  They  aid  in 
the  absorption  of  fats  from  the  intestine.  (3)  They  aid  in  the  absorption  of 
peptones  from  the  inte-tine.  It  maybe  noticed  here  that  these  theories  apply 
to  the  leucocytes  found  SO  abundantly  in  the  lymphoid  tissue  of  the  aliment- 
ary canal,  rather  than  to  those  contained  in  the  blood  itself.  (4)  They  take 
pari  in  the  process  of  blood-coagulation.  A  complete  statement  with  refer- 
ence to  this  function  must  be  reserved  until  the  phenomenon  of  coagulation  is 


BLOOD.  49 

described.  (5)  They  help  to  maintain  the  normal  composition  of  the  blood- 
plasma  as  to  its  proteids.  It  may  be  said  for  this  view  that  there  is  considerable 
evidence  to  show  that  the  leucocytes  normally  undergo  disintegration  and  dis- 
solution in  the  circulating  blood,  to  some  extent  at  least.  The  blood-proteids 
are  peculiar,  and  they  are  not  formed  directly  from  the  digested  food.  It  is 
possible  that  the  leucocytes,  which  are  the  only  typical  cells  in  the  blood,  aid 
in  keeping  up  the  normal  supply  of  proteids.  From  this  standpoint  they 
might  be  regarded  in  fact  as  unicellular  glands,  the  products  of  their  metab- 
olism serving  to  maintain  the  normal  composition  of  the  blood-plasma. 
The  formation  of  granules  within  the  substance  of  the  eosinophiles  offers  a 
suggestive  analogy  to  the  accumulation  of  zymogen  granules  in  glandular 
cells.  As  to  the  origin  of  the  leucocytes,  it  is  known  that  they  increase  in 
number  while  in  the  circulation,  undergoing  multiplication  by  karyokinesis ; 
but  the  greater  number  are  probably  produced  in  the  lymph-glands  and  in 
the  lymphoid  tissue  of  the  body,  whence  they  get  into  the  lymph-stream  and 
eventually  are  brought  into  the  blood. 

Physiology  of  the  Blood-plates. — The  blood-plates  are  small  circular 
or  elliptical  bodies,  nearly  homogeneous  in  structure  and  variable  in  size  (0.5  to 
5.5//),  but  they  are  always  smaller  than  the  red  corpuscles  (see  Histology).  Less 
is  known  of  their  origin,  fate,  and  functions  than  in  the  case  of  the  leucocytes. 
It  is  certain  that  they  are  not  independent  cells,  and  it  is  altogether  probable, 
therefore,  that  they  soon  disintegrate  and  dissolve  in  the  plasma.  When 
removed  from  the  circulating  blood  they  are  known  to  disintegrate  very 
rapidly.  This  peculiarity,  in  fact,  prevented  them  from  being  discovered  for 
a  long  time  after  the  blood  had  been  studied  microscopically.  Recent  work 
has  shown  that  they  are  formed  elements,  and  not  simply  precipitates  from  the 
plasma,  as  was  suggested  at  one  time.  The  theory  of  Hayem,  their  real 
discoverer,  that  they  develop  into  red  corpuscles  may  also  be  considered  as 
erroneous.  There  is  considerable  evidence  to  show  that  in  shed  blood  they 
take  part  in  the  process  of  coagulation.  The  nature  of  this  evidence  will  be 
described  later. 

Lilienfeld1  has  claimed  that  chemically  the  blood-plates  contain  a  nucleo- 
albumin  (see  section  on  Chemistry  of  the  Body),  to  which  he  gives  the  specific 
name  of  "nucleohiston."  The  same  substance  is  contained  in  the  nuclei  of 
leucocytes.  This  latter  fact  may  be  taken  as  additional  evidence  for  a  view 
which  has  already  been  supported  on  morphological  grounds — that  the  blood- 
plates  are  derived  from  the  nuclei  of  the  leucocytes.  According  to  this 
theory  when  the  polynuclear  leucocytes  go  to  pieces  in  the  blood  the  frag- 
ments of  nuclei  contained  in  them  persist  for  a  longer  or  shorter  time  as 
blood-plates,  that  in  time  eventually  dissolve  in  the  plasma.  If  this  last 
statement  is  correct,  then  it  follows  that  the  substance  contained  in  the  blood- 
plates  either  goes  to  form  one  of  the  normal  constituents  of  the  plasma,  useful 
in  nutrition  or  otherwise,  or  that  it  forms  a  waste  product  that  is  eliminated 
from  the  body. 

1  Da  Bois-lleymond's  Archiv  fiir  Physiologic,  1893,  S.  5G0. 
Vol.  I.— 4 


oO 


AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 


B.  Chemical  Composition  of  the  Blood  ;  Coagulation;  Total 
Quantity  of  Blood  ;  Regeneration  after  Hemorrhage. 

Composition  of  the  Plasma  and  Corpuscles. — Blood  (plasma  and  cor- 
puscle-) contains  a  great  variety  of  substances,  as  may  be  inferred  from  its 
double  relation-  to  tin4  tissues  as  a  source  of  food-supply  and  as  a  means  of 
removing  the  waste  products  of  their  functional  activity.  The  constituents 
existing  in  quantities  sufficiently  large  for  recognition  by  chemical  means  are 
as  follows:  (lj  Water j  (2)  proteids,  of  which  three  varieties  at  least  are 
known  to  exist  in  the  plasma — namely,  fibrinogen,  paraglobulin  (serum- 
globulin),  and  serum-albumin;  (3)  combined  proteids  (haemoglobin,  nucleo- 
albumins)  j  (I)  extractives,  including  such  substances  as  fats,  sugar,  urea, 
lecithin,  cholesterin,  etc.;  and  (5)  inorganic  salts.  The  proportions  of  these 
substances  found  in  the  blood  of  various  mammals  differ  somewhat,  although 
the  qualitative  composition  is  practically  the  same  in  all. 

'I  lie  following  tables,  taken  from  different  sources,  summarize  the  general 
result-  of  the  quantitative  analyses  made  by  several  observer-: 


Analysis  of  the  Whole  Blood,  Human  (C.  Schmidt). 


Water 

Solids      

Proteids  and  extractives 

Fibrin  (derived  from  the  fibrinogen) 

I  lamatin  (and  iron) 

Salts         


Man 

Woman 

(25  years). 

(30  years.) 

788.71 

824.55 

211.29 

175.45 

191.78 

157.93 

3.93 

1.91 

7.7(1 

6.99 

7.88 

8.62 

Inorganic  Sails  of  Human  Blood,  1000  parts  (C.  Schmidt). 


Blood-corpnscles. 
CI 1.75 

i<  i  > 3.091 

Na20 0.470 

S03        0.061 

P265 1.355 

CaO 

MgO 


Blood-plasma. 

CI 3.536 

K20 0.314 

Na20 3.410 

so      0.129 

I '.<>., 0.145 

CaO 

MgO ■    . 


These  acids  and  bases  exist,  of  course,  in  the  plasma  and  the  corpuscles  as 
salts.  It  is  not  possible  to  determine  exactly  how  they  are  combined  as  salts, 
but  Schmidt  suggests  the  following  probable  combinations: 


Probable  Salts  in  the  Corpuscles. 

Potassium  sulphate 0.132 

Potassium  chloride 3.679 

Potassium  phosphate 'J..".!:; 

Sodium  phosphate 0.633 

ira  carbonate 0.3  tl 

<  'alcium  phosphate 0.09  I 

Magnesium  phosphate  ....  0.060 


Probable  salt-  in  the  Plasma. 

Potassium  sulphate 0.281 

Potassium  chloride 0.359 

Sodium  chloride 5.5  16 

Sodium  phosphate 0.271 

Sodium  carbonate 1.532 

<  alcium  phosphate 0.298 

Magnesium  phosphate  ....  0.218 


BLOOD. 


51 


One  interesting  fact  brought  out  in  the  above  table  is  the  peculiarity  in 

distribution  of  the  potassium  and  sodium  salts  between  the  plasma  and  the 
corpuscles.  The  plasma  contains  an  excess  of  the  total  sodium  salts,  and  the 
corpuscles  contain  an  excess  of  the  potassium  salts. 


Composition  of  Blood-plasma  (1000  parts). 


Water 

Solids  . 

Total  proteids 

Fibrin  (derived  from  the  fibrinogen 

Paraglobidin 

Serum-albumin 

Extractives  and  salts 


Horse. 


917.6 
82.4 
69.5 
6.5 
38.4 
24.6 
12.9 


Composition  of  Blood-serum  (1000  parts).1 


Horse. 


85.97 
72.57 

45.65 
26.92 
13.40 


Man. 


92.07 
76.20 

31.04 
45.16 

15.88 


Ox. 


89.65 
74.99 

41.69 
33.30 
14.66 


Bed  Corpuscles,  Human  Blood  (Hoppe-Seyler). 

I.  II. 

Oxyhemoglobin 86.8  94.3  per  cent. 

Proteid  (and  nuclein  ?) 12.2         5.1 

Lecithin      0.7         0.4       " 

Cbolesterin 0.3         0.3       " 

Leucocytes,  Thymus  of  Calf  (Lilienfeld). 
In  the 'total  dry  substance  of  the  corpuscles,  which  was  equal  to  11.49  per  cent.,  there  were  contained — 

Proteid 1.76  per  cent. 

Leuco-nuclein 68.78       " 

Histon 8.67 

Lecithin 7.51       " 

Fat 4.02       " 

Cholesterin 4.40       " 

Glycogen 0.S0       " 

The  extractives  present  in  the  blood  vary  in  amount  under  different  conditions. 
Average  estimates  of  some  of  them,  given  in  percentages  of  the  entire  blood, 
have  been  reported  as  follows : 

Dextrose  (grape-sugar) 0.117  percent. 

Urea 0.016 

Lecithin 0.0844     " 

Cholesterin 0.041       " 

Proteids  of  the  Blood-plasma. — The  properties  and  reactions  of  proteids 
and  the  related  compounds,  as  well  as  a  classification  of  those  occurring  in  t lie 
animal  body,  are  described  in  the  section  on  the  Chemistry  of  the  Body. 
This  description  should  be  read  before  attempting  to  study  the  proteids  of 
the  plasma  and  the  part  they  take  in  coagulation.  Three  proteids  are  usually 
described  as  existing  in  the  plasma  of  circulating  blood — namely,  fibrinogen, 
paraglobulih,  or,  as  it  is  sometimes  called,  "serum-globulin,"  and  serum-albu- 
min. The  first  two  of  these  proteids,  fibrinogen  and  paraglobidin,  belong  to 
the  group  of  globulins,  and  hence  have  many  properties  in  common.  Serum- 
albumin  belongs  to  the  group  of  so-called  ''native  albumins"  of  which  egg- 
albumin  constitutes  another  member. 

1  Haramarsten  :   .1  Text-book  of  Physiological  Chemistry,  1898  [translated  by  Mandel). 


52  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

Serum-albumin. — This  substance  is  a  typical  proteid.  It  can  be  obtained 
readily  in  crystalline  form.  Its  percentage  composition,  according  to  Hara- 
marsten,  is  as  follows  :  C  53.06,  H  6.85,  N  16.04,  S  1.80,  O  22.26. 

Its  molecular  composition,  according  to  Schmiedeberg,1  may  be  represented 
by  C'.J  1  ,.,,\  ,,,S( ),(  or  some  multiple  of  this  formula.  Serum-albumin  shows  the 
general  reactions  of  the  native  albumins.  One  of  its  most  useful  reactions  is 
its  behavior  toward  magnesium  sulphate.  Serum-albumin  usually  occurs  in 
liquids  together  with  the  globulins,  as  is  the  case  in  blood.  If  such  a  liquid 
is  thoroughly  saturated  with  solid  MgS04,  the  globulins  are  precipitated  com- 
pletely, while  the  albumin  is  not  affected.  So  far  as  the  blood  and  similar 
liquids  are  concerned,  a  definition  of  serum-albumin  might  be  given  by  saying 
that  it  comprises  all  the  proteids  not  precipitated  by  MgS04.  When  its 
solutions  have  a  neutral  or  an  acid  reaction,  serum-albumin  is  precipitated  in 
an  insoluble  form  by  heating  the  solution  above  a  certain  degree.  Precipi- 
tates produced  in  this  way  by  heating  solutions  of  proteids  are  spoken  of 
as  coagulations — heat  coagulations — and  the  exact  temperature  at  which 
coagulation  occurs  is  to  a  certain  extent  characteristic  for  each  proteid.  The 
temperature  of  coagulation  of  serum-albumin  is  usually  given  at  from  70° 
to  75°  C,  but  it  varies .  greatly  with  the  conditions.  It  has  been  asserted, 
in  fact,  that  careful  heating  under  proper  conditions  gives  separate  coagula- 
tions at  three  different  temperatures — namely,  73°,  77°,  and  84°  C. — indi- 
cating the  possibility  that  what  is  called  "  serum-albumin  "  may  be  a  mixture 
of  three  proteids.  Serum-albumin  occurs  in  blood-plasma  and  blood-serum, 
in  lymph,  and  in  the  different  normal  and  pathological  exudations  found  in  the 
body,  such  as  pericardial  liquid,  hydrocele  fluid,  etc.  The  amount  of  serum- 
albumin  in  the  blood  varies  in  different  animals,  ranging  among  the  mam- 
malia from  2.67  per  cent,  in  the  horse  to  4.52  per  cent,  in  man.  In  some 
of  the  cold-blooded  animals  it  occurs  in  surprisingly  small  quantities — 
0.36  to  0.69  per  cent.  As  to  the  source  or  origin  of  serum-albumin,  it  is 
frequently  stated  that  it  comes  from  the  digested  proteids  of  the  food.  It 
is  known  that  proteid  material  in  the  food  is  not  changed  at  once  to  serum- 
albumin  during  the  act  of  digestion ;  indeed,  it  is  known  that  the  final  product 
of  digestion  is  a  proteid  or  group  of  proteids  of  an  entirely  different  character — 
namely,  peptones  and  proteoses ;  but  during  the  act  of  absorption  into  the 
blood  these  latter  bodies  are  supposed  to  undergo  transformation  into  serum- 
albumin.  From  a  physiological  standpoint  serum-albumin  is  considered  to  be 
the  main  source  of  proteid  nourishment  for  the  tissues  generally.  As  will  be 
explained  in  the  section  on  Nutrition,  one  of  the  most  important  requisites  in 
the  nutrition  of  the  cells  of  the  body  is  an  adequate  supply  of  proteid  material 
to  replace  that  used  up  in  the  chemical  changes,  the  metabolism,  of  the  tissues. 
Serum-albumin  is  supposed  to  furnish  a  part,  at  least,  of  this  supply, 
although  as  a  matter  of  fact  there  is  no  substantial  proof  that  this  view  is 
correct.  As  long  as  the  serum-albumin  is  in  the  blood-vessels  it  is,  of  course, 
cut  off  from  the  tissues.  The  cells,  however,  are  bathed  directly  in  lymph, 
1  Archivjur  exper.  Pathol,  u.  PhannakoL,  1897,  Bd.  39,  S.  1. 


BLOOD.  53 

and  this  in  turn  is  formed  from  the  plasma  of  the  blood  which  is  transuded, 
or,  according  to  some  physiologists,  secreted,  through  the  vessel-walls. 

Paraglobulin,  which  belongs  to  the  group  of  globulins,  exhibits  the  general 
reactions  characteristic  of  the  group.  As  stated  above,  it  is  completely  pre- 
cipitated from  its  solutions  by  saturation  with  MgS04.  It  is  incompletely  pre- 
cipitated by  saturation  with  common  salt  (NaCl).  In  neutral  or  feebly  acid 
solutions  it  coagulates  upon  heating  to  75°  C.  Hammarsten  gives  its  percentage 
composition  as— C  52.71,  H7.01,  N  15.85,  S  1.11,  O  23.24.  Schmiedeberg 
gives  it  a  molecular  composition  corresponding  to  the  formula  0,^11, ^N^SO^ 
+  ^H20.  According  to  Faust,1  the  precipitate  of  paraglobulin  usually  obtained 
with  MgS04  contains  a  certain  amount  of  an  albuminoid  body,  glutolin,  which  he 
believes  to  be  a  constant  constituent  of  blood-plasma.  Paraglobulin  occurs  in 
blood,  in  lymph,  and  in  the  normal  and  pathological  exudations.  The  amount 
of  paraglobulin  present  in  blood  varies  in  different  animals.  Among  the  mam- 
malia the  amount  ranges  from  1.78  per  cent,  in  rabbits  to  4.56  per  cent,  in  the 
horse.  In  human  blood  it  is  given  at  3.10  per  cent.,  being  less  in  amount, 
therefore,  than  the  serum-albumin.  It  will  be  seen,  upon  examining  the 
tables  of  composition  of  the  blood-plasma  and  blood-serum  of  the  horse 
(p.  51),  that  more  of  this  proteid  is"  found  in  the  serum  than  in  the  plasma. 
This  result,  which  is  usually  considered  as  being  true,  is  explained  by  supposing 
that  during  coagulation  some  of  the  leucocytes  disintegrate  and  part  of  their 
substance  passes  into  solution  as  a  globulin  identical  with  or  closely  resembling 
paraglobulin.  The  figures  given  above  show  that  a  considerable  amount  of 
paraglobulin  is  normally  present  in  blood.  It  is  reasonable  to  suppose  that, 
like  serum-albumin,  this  proteid  is  valuable  as  a  source  of  nitrogenous  food 
to  the  tissues.  It  is  uncertain,  however,  whether  it  is  used  by  the  tissues 
directly  as  paraglobulin  or  is  first  converted  into  some  other  form  of  proteid. 
It  is  entirely  unknown,  also,  whether  its  value  as  a  proteid  supply  is  in  any 
way  different  from  that  of  serum-albumin.  The  origin  of  paraglobulin 
remains  undetermined.  It  may  arise  from  the  digested  proteids  absorbed 
from  the  alimentary  canal,  but  there  is  no  evidence  to  support  such  a  view. 
Another  suggestion  is  that  it  comes  from  the  disintegration  of  the  leucocytes 
(and  other  formed  elements)  of  the  blood.  These  bodies  are  known  to  contain 
a  small  quantity  of  a  globulin  resembling  paraglobulin,  and  it  is  possible  that 
this  globulin  may  be  liberated  after  the  dissolution  of  the  leucocytes  in  the 
plasma,  and  thus  go  to  make  up  the  normal  supply  <>i*  paraglobulin.  The 
fact  remains,  however,  that  at  present  the  origin  and  the  special  use  of  the 
paraglobulin  are  entirely  unknown. 

Fibrinogen  is  a  proteid  belonging  to  the  globulin  class  and  exhibiting  all 
the  general  reactions  of  this  group.  It  is  distinguished  from  paraglobulin  by 
a  number  of  special  reactions;  for  example,  its  temperature  of  heat  coagula- 
tion is  much  lower  (50°  to  60°  C),  and  it  is  completely  thrown  down  from  its 
solutions  by  saturation  with  NaCl  as  well  as  with  MgS04.  It-  most  impor- 
tant and  distinctive  reaction  is,  however,  that  under  proper  conditions  it  gives 
'Faust,  Inaugural  Dissertation,  Leipzig,  L898, 


54  AN  AMERICAN    TEXT-HOOK    OE   PHYSIOLOGY. 

rise  to  an  insoluble  proteid,  fibrin,  whose  formation  is  the  essential  phenom- 
enon in  the  coagulation  of  blood.  Fibrinogen  has  a  percentage  composition, 
according  to  Eammarsten,  of— C  52.93,  H  6.90,  N  16.66,  S  1.25,  ()  22.26; 
while  its  molecular  composition,  according  to  Schmiedeberg,  is  indicated  by 
the  formula  C^gH^gN^SO^. 

Fibrinogen  is  found  in  blood-plasma,  lymph,  and  in  some  cases,  though  not 
always,  in  the  normal  and  pathological  exudations.  It  is  absent  from  blood- 
serum,  being  used  up  during  the  process  of  clotting.  It  occurs  in  very  small 
quantities  in  blood,  compared  with  the  other  proteids.  There  is  no  good 
method  of  determining  quantitatively  the  amount  of  fibrinogen,  but  estimates 
of  the  amount  of  fibrin,  which  cannot  differ  very  much  from  the  fibrinogen, 
show  that  in  human  blood  it  varies  from  0.22  to  0.4  per  cent.  In  horse's 
blood  it  may  be  more  abundant — 0.65  per  cent.  As  to  the  origin  and  the 
special  physiological  value  of  this  proteid  we  are,  if  possible,  more  in  the  dark 
than  in  the  case  of  paraglobulin,  with  the  exception  that  fibrinogen  is  known  to 
be  the  source  of  the  fibrin  of  the  blood.  But  clotting  is  an  occasional  phe- 
nomenon only.  What  nutritive  function,  if  any,  is  possessed  by  fibrinogen 
under  normal  conditions  is  unknown.  No  satisfactory  account  has  been  given 
of  its  origin.  It  has  been  suggested  by  different  investigators  that  it  may 
come  from  the  nuclei  of  disintegrating  leucocytes  (and  blood-plates)  or  from 
the  dissolution  of  the  extruded  nuclei  of  newly-made  red  corpuscles,  but  here 
again  we  have  only  speculations,  that  cannot  be  accepted  until  some  experi- 
mental proof  is  advanced  to  support  them. 

Coagulation  of  Blood. — One  of  the  most  striking  properties  of  blood  is 
its  power  of  clotting  or  coagulating  shortly  after  it  escapes  from  the  blood- 
vessels. The  general  changes  in  the  blood  during  this  process  are  easily  fol- 
lowed. At  first  shed  blood  is  perfectly  fluid,  but  in  a  few  minutes  it  becomes 
viscous  and  then  sets  into  a  soft  jelly  which  quickly  becomes  firmer,  so  that 
the  vessel  containing  it  can  be  inverted  without  spilling  the  blood.  The  clot 
continues  to  grow  more  compact  and  gradually  shrinks  in  volume,  pressing  out 
a  smaller  or  larger  quantity  of  a  clear,  faintly  yellow  liquid  to  which  the  name 
blood-serum  has  been  given.  The  essential  part  of  the  clot  is  the  fibrin.  Fibrin 
is  an  insoluble  proteid  that  is  absent  from  normal  blood.  In  shed  blood,  and 
under  certain  conditions  in  blood  while  still  in  the  blood-vessels,  this  fibrin 
is  formed  from  the  soluble  fibrinogen.  The  deposition  of  the  fibrin  is  peculiar. 
It  i-  precipitated,  if  the  word  maybe  used,  in  the  form  of  an  exceedingly  fine 
network  of  delicate  threads  that  permeate  the  whole  mass  of  the  blood  and 
give  the  clot  its  jelly-like  character.  The  shrinking  of  the  threads  causes 
the  subsequent  contraction  of  the  clot.  If  the  blood  has  not  been  shaken 
during  the  act  of  clotting,  almost  all  the  red  corpuscles  are  caught  in  the  line 
fibrin  meshwork,  and  as  the  clot  shrinks  these  corpuscles  are  held  more  firmly, 
only  the  clear  liquid  of  the  blood  being  squeezed  out,  so  that  it  is  possible  to 
get  specimens  of  serum  containing  few  or  no  red  corpuscles.  The  leucocytes, 
on  the  contrary,  although  they  arc  also  caught  at  first  in  .the  forming  mesh- 
work of  fibrin,  may  readily  pass  out  into  the  serum  in  the  later  stages  of  clot- 


BLOOD.  55 

ting,  on  account  of  their  power  of  making  amoeboid  movements.  It'  the  blood 
has  been  agitated  during  the  process  of  clotting,  the  delicate  network  will  be 
broken  in  places  and  the  scrum  will  be  more  or  less  bloody — that  is,  it  will 
contain  numerous  red  corpuscles.  If  during  the  time  of  clotting  the  blood  is 
vigorously  whipped  with  a  bundle  of  fine  rods,  all  the  fibrin  will  be  deposited 
as  a  stringy  mass  upon  the  whip,  and  the  remaining  liquid  part  will  consist  of 
serum  plus  the  blood-corpuseles.  Blood  that  has  been  whipped  in  this  way 
is  known  as  "  defibrinated  blood."  It  resembles  normal  blood  in  appearance, 
but  is  different  in  its  composition:  it  cannot  clot  again.  The  way  in  which 
the  fibrin  is  normally  deposited  may  be  demonstrated  most  beautifully  under 
the  microscope  by  placing  a  good-sized  drop  of  blood  on  a  slide,  covering  it 
with  a  cover-slip,  and  allowing  it  to  stand  for  several  minutes  until  coagu- 
lation is  completed.  If  the  drop  is  now  examined,  it  is  possible  by  careful 
focussing  to  discover  in  the  spaces  between  the  masses  of  corpuscles  many 
examples  of  the  delicate  fibrin  network.  The  physiological  value  of  clotting 
is  that  it  stops  hemorrhages  by  closing  the  openings  of  the  wounded  blood- 
vessels. 

Time  of  Clotting. — The  time  necessary  for  the  clot  to  form  varies  slightly 
in  different  individuals,  or  in  the  blood  of  the  same  individual  varies  with  the 
conditions.  It  may.be  said  in  general  that  under  normal  conditions  the  blood 
passes  into  the  jelly  stage  in  from  three  to  ten  minutes.  The  separation  of 
clot  and  serum  takes  [dace  gradually,  but  is  usually  completed  in  from  ten  to 
forty-eight  hours.  The  time  of  clotting  shows  marked  variations  in  different 
animals;  the  process  is  especially  slow  in  the  horse  and  the  terrapin,  so  that 
coagulation  of  shed  blood  is  more  easily  prevented  in  these  animals.  In  the 
human  being  also  the  time  of  clotting  may  be  much  prolonged  under  certain 
conditions — in  fevers,  for  example.  This  fact  was  noticed  in  the  days  when 
bloodletting  was  a  common  practice.  The  slow  clotting  of  the  blood  permitted 
the  red  corpuscles  to  sink  somewhat,  so  that  the  upper  part  of  the  clot  in  such 
cases  was  of  a  lighter  color,  forming  what  was  called  the  "  buffy  coat."  The 
time  of  clotting  may  be  shortened  or  be  prolonged,  or  the  clotting  may  be  pre- 
vented altogether,  in  various  ways,  and  much  use  has  been  made  of  this  fact 
in  studying  the  composition  and  the  coagulation  of  blood  as  well  as  in  con- 
trolling hemorrhages.  It  will  be  advantageous  to  postpone  an  account  of  these 
methods  for  hastening  or  retarding  coagulation  until  the  theories  of  coagulation 
have  been  considered. 

Theories  of  Coagulation. — The  clotting  of  blood  is  such  a  prominent  phe- 
nomenon that  it  has  attracted  attention  at  all  times,  and  as  a  result  numerous 
theories  to  account  for  it  have  been  advanced.  Most  of  these  theories  possess 
simply  an  historical  interest,  and  need  not  be  discussed  in  a  work  of  this  charac- 
ter, but  some  reference  to  older  views  is  unavoidable  for  a  proper  presentation 
of  the  subject.  To  prevent  misunderstanding  it  may  he  stated  explicitly  in 
the  beginning  that  there  is  at  present  no  perfectly  satisfactory  theory.  Indeed, 
the  subject  is  a  difficult  one,  as  it  is  intimately  connected  with  the  chemistry 
of  the  proteids  of  the  blood,  and  it  may  lie  said  that  a  complete  understanding 


56  AN  AMERICAN    TENT-BOOK   OF  PHYSIOLOGY. 

of  clotting  waits  upon  a  better  knowledge  of  the  nature  of  these  proteids.  It 
is  possible  that  at  any  moment  new  facts  may  be  discovered  that  will  alter 
present  ideas  of  the  nature  of  the  process.  In  considering  the  different 
theories  that  have  been  proposed  there  are  two  general  facts  that  should 
always  be  kept  in  mind  :  first,  that  the  main  phenomenon  that  a  theory  of 
coagulation  has  to  explain  is  the  formation  of  fibrin  ;  second,  that  all  theories 
unite  in  the  common  belief  that  the  fibrin  is  derived,  in  part,  at  least,  from 
the  fibrinogen  of  the  plasma. 

Schmidt's  Older  Theory  of  <  'oagulation. — The  first  theory  that  gained 
general  acceptance  in  recent  times  was  that  of  Alexander  Schmidt.  It  was 
proposed  in  1861,  and  it  has  served  as  the  basis  for  all  subsequent  theories. 
Schmidt  held  that  the  fibrin  of  the  clot  is  formed  by  a  reaction  between  para- 
globulin  (he  called  it  "  fibrinoplastin  ")  and  fibrinogen,  and  that  this  reaction  is 
brought  about  by  a  third  body,  to  which  he  gave  the  name  of  fibrin  ferment. 
Fibrin  ferment  was  believed  to  be  absent  from  normal  blood,  but  to  be  formed 
after  the  blood  was  shed.  Further  reference  will  presently  be  made  to  the 
nature  of  this  substance.  Schmidt  was  not  able  to  determine  its  nature — 
whether  it  was  a  proteid  or  not — but  he  discovered  a  method  of  preparing  it 
from  blood-serum,  and  demonstrated  that  it  cannot  be  obtained  from  blood 
immediately  after  it  leaves  the  blood-vessels,  and  that  consequently  it  does  not 
exist  in  circulating  blood,  in  any  appreciable  quantity  at  least.  Finally, 
Schmidt  believed  that  a  certain  quantity  of  soluble  salts  is  necessary  as  a 
fourth  "  fibrin  factor." 

Uammarsten's  Theory  of  Coagulation. — Hammarsten,  who  repeated 
Schmidt's  experiments,  demonstrated  that  paraglobulin  is  unnecessary  for 
the  formation  of  fibrin.  He  showed  that  if  a  solution  of  pure  fibrinogen  is 
prepared,  and  if  there  is  added  to  it  a  solution  of  fibrin  ferment  entirely  free 
from  paraglobulin,  a  typical  clot  is  formed.  This  experiment  has  since  been 
confirmed  by  others,  so  that  at  present  it  is  generally  accepted  that  paraglob- 
ulin takes  no  direct  part  in  the  formation  of  fibrin.  Hammarsten's  theory 
was  that  there  are  two  fibrin  factors,  fibrin  ferment  and  fibrinogen,  and  that 
fibrin  results  from  a  reaction  between  these  two  bodies.  The  nature  of  this 
reaction  could  not  be  determined,  but  Hammarsten  showed  that  the  entire 
fibrinogen  molecule  is  not  changed  to  fibrin.  In  place  of  the  fibrinogen 
there  is  present  after  clotting,  on  the  one  hand,  fibrin  representing  most  of 
the  weight  of  fibrinogen  (60-90  per  cent.),  and,  on  the  other  hand,  a  newly- 
formed  globulin-like  proteid  retained  in  solution  in  the  serum,  to  which  pro- 
teid  the  name  fibrin-globulin  has  been  given.  Hammarsten  supposed  that 
although  paraglobulin  took  no  direct  part  in  the  process,  it  acted  as  a  favor- 
ing condition,  a  greater  quantity  of  fibrin  being  formed  when  it  was  present. 
Later  experiments1  indicated  that  this  supposition  was  incorrect,  and  that 
paraglobulin  may  be  eliminated  entirely  trom  the  theory.  The  theory  of 
Hammarsten,  which  is  perhaps  generally  accepted  at  the  present  time,  is 
incomplete,  however,  in  that  it  have.-  undetermined  the  nature  of  the  ferment 
1  Frederikse:  Zeitschrift  fur  physioloyische  Chemie,  lid.  19,  1814,  S.  143. 


BLOOD.  57 

and  of  the  reaction  between  it  and  fibrinogen.     The  aim  of  the  newer  theories 
has  been  to  supply  this  deficiency. 

Schmidt's  Theory  of  Coagulation. — In  a  volume1  containing  the  re- 
sults of  a  lifetime  of  work  devoted  to  the  study  of  blood-coagulation, 
Schmidt  has  modified  his  well-known  theory.  His  present  ideas  of  the  direct 
and  indirect  connection  of  the  proteids  of  the  plasma  with  the  formation  of 
fibrin  are  too  complex  to  be  stated  clearly  in  brief  compass.  He  classifies  the 
conditions  necessary  for  coagulation  as  follows  :  (1)  Certain  soluble  proteids — 
namely,  the  two  globulins  of  the  blood — as  the  material  from  which  fibrin  is 
made.  Schmidt  does  not  believe,  however,  that  paraglobulin  and  fibrinogen 
react  to  make  fibrin,  but  believes  that  fibrinogen  is  formed  from  paraglobulin, 
and  that  fibrinogen  in  turn  is  changed  to  fibrin.  (2)  A  specific  ferment,  fibrin 
ferment,  to  eifect  the  changes  in  the  proteids  just  stated.  He  proposes  for 
fibrin  ferment  the  distinctive  name  of  thrombin.  (3)  A  certain  quantity  of 
neutral  salts  is  necessary  for  the  precipitation  of  the  fibrin  in  an  insoluble  form. 

The  Relation  of  Calcium  Salts  to  Coagulation. — It  has  been  shown  by  a 
number  of  observers  that  calcium  salts  take  an  important  part  in  the  pro- 
cess of  clotting.  This  fact  was  first  clearly  demonstrated  by  Arthus  and 
Pages,  who  found  that  if  oxalate  of  potash  or  soda  is  added  to  freshly-drawn 
blood  in  quantities  sufficient  to  precipitate  the  calcium  salts,  clotting  will  be 
prevented.  If,  however,  a  soluble  calcium  salt  is  again  added,  clotting  occurs 
promptly.  This  fact  has  been  demonstrated  not  only  for  the  blood,  but  also 
for  pure  solutions  of  fibrinogen,  and  we  are  justified  in  saying  that  without 
the  presence  of  calcium  salts  fibrin  cannot  be  formed  from  fibrinogen.  This 
is  one  of  the  most  significant  facts  recently  brought  out  in  connection  with 
coagulation.  We  know  that  fibrinogen  when  acted  upon  by  fibrin  ferment 
produces  fibrin,  but  we  now  know  also  that  calcium  salts  must  be  present. 
What  is  the  relation  of  these  salts  to  the  so-called  "ferment"?  The  most 
explicit  theory  proposed  in  answer  to  this  question  we  owe  to  Pekelharing. 

Pekelha ring's  Theory  of  Coagulation. — Pekelharing-  succeeded  in  sepa- 
rating from  blood-plasma  a  proteid  body  that  has  the  properties  of  a  nucleo- 
albumin.  He  finds  that  if  this  substance  is  brought  into  solution  together 
with  fibrinogen  and  calcium  salts,  a  typical  clot  will  form,  while  nueleo- 
albumin  alone,  or  calcium  salts  alone,  added  to  fibrinogen  solutions,  cause 
no  clotting.  His  theory  of  coagulation  is  that  what  has  been  called  "fibrin 
ferment"  is  a  compound  of  nucleo-albumin  and  calcium,  and  that  when 
this  compound  is  brought  into  contact  with  fibrinogen  a  reaction  occurs,  the 
calcium  passing  over  to  the  fibrinogen  and  forming  an  insoluble  calcium 
compound,  fibrin.  According  to  this  theory,  fibrin  is  a  calcium  compound 
with  fibrinogen  or  with  a  part  of  the  fibrinogen  molecule.  This  idea  is 
strengthened  by  the  unusually  large  percentage  of  calcium  found  in  fibrin 
ash.  The  theory  supposes  also  that  the  fibrin  ferment  is  not  present  in  blood- 
plasma — that  is,  in  sufficient  quantity  to  set  up  coagulation — but  that  it  is  formed 

1  Zwr  Blutlehre,  Leipzig  1893. 

2  lTnttrsiirliu)it/rn    iibcr  (lax  Fibriiifcnnrnt,  Amsterdam,   1S<)'J. 


58  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

after  the  blood  is  shed.  The  nucleo-albumio  part  is  derived  faom  the  cor- 
puscles of  the  blood  (leucocytes,  blood-plates),  which  break  down  and  go  into 
solution.  This  nucleo-albumin  then  unites  with  the  calcium  salts  present  in 
the  blood  to  form  fibrin  ferment,  an  organic  compound  of  calcium  capable  of 
reacting  with  fibrinogen.  The  theory  is  a  simple  one  ;  it  accounts  tor  the 
importance  of  calcium  salts  in  coagulation,  and  reduces  the  interchange  be- 
tween fibrinogen  and  fibrin  ferment  to  the  nature  of  an  ordinary  chemical 
reaction;  but  it  cannot  be  accepted  without  reservation  at  present,  since  the 
experimental  evidence  is  not  entirely  in  its  favor.  Hammarsten,  for  instance, 
in  some  careful  experiments  seems  to  have  obtained  facts  that  are  at  variance 
with  a  part  at  least  of  this  theory.  Hammarsten1  states  that  blood-plasma 
or  fibrinogen  solutions  to  which  an  excess  of  potsssium  oxalate  had  been 
added,  and  which  therefore  was  free  presumably  from  precipitable  calcium 
salts,  underwent  typical  coagulation  when  mixed  with  blood-serum  to  which  an 
excess  of  oxalate  had  also  been  added.  In  other  words,  a  solution  of  fibrinogen 
free  from  calcium  reacted  with  a  solution  of  fibrin  ferment  (blood-serum)  also 
apparently  free  from  calcium.  It  might  be  urged  against  this  experiment, 
however,  that  in  the  blood-serum  used  the  combination  of  calcium  and  nucleo- 
proteid  to  form  ferment  had  already  taken  place, and  that  in  this  combination 
the  calcium  is  not  acted  upon  by  the  oxalate.  Hammarsten  indeed  admits  that 
something  of  this  kind  may  occur,  for  he  is  convinced,  like  others,  that  calcium 
in  some  way  is  essential  to  coagulation,  his  suggestion  being  that  it  plays  an  un- 
known part  in  the  formation  of  the  ferment.  He  supposes  that  in  the  plasma 
of  shed  blood  a  material  is  present  which  he  designates  as  prothrombin,  and 
the  calcium  in  some  way  converts  this  into  the  active  ferment,  the  thrombin. 
According  to  the  more  explicit  hypothesis  of  Pekelharing,  the  prothrombin  is 
a  form  of  nucleo-proteid  and  the  thrombin  a  calcium  compound  of  this  pro- 
teid.  The  second  part  of  IVkelharing's  theory,  namely,  that  the  reaction 
between  the  ferment  and  the  fibrinogen  consists  in  a  transfer  of  the  calcium 
from  the  former  to  the  latter,  is  directly  contradicted  by  Ilammarsten's  experi- 
ments. Quantitative  analysis  of  fibrinogen  and  fibrin  showed  that  the  latter 
docs  not  contain  any  larger  amount  of  calcium  than  the  former.  This  author 
is  inclined  to  consider  the  (  a  contained  in  fibrin  of  the  nature  of  an  impurity, 
and  not  as  an  essential  constituent  of  the  fibrin  molecule.  By  the  use  of 
special  methods  he  has  succeeded  in  obtaining  typical  fibrin  containing  as 
little  as  0.005  per  cent,  of  ('a.  We  must  be  content  to  say  that  in  the  clot- 
ting of  blood  three  factors  are  necessary — namely,  the  fibrinogen  and  the 
calcium  salts  of  plasma,  which  are  present  in  the  circulating  blood,  and  the 
fibrin  ferment,  which  is  formed  after  the  blood  is  shed. 

Nature  and  Origin  of  Fibrin  Ferment  (Thrombin). — Recent  views  as 
to  the  nature  of  fibrin  ferment  have  been  referred  to  incidentally  in  the 
description  of  the  theories  of  coagulation  just  given.  The  relation  of  these 
newei'  views  to  the  older  idea-  can  be  presented  most  easily  by  giving  a 
brief  description  of  the  development  of  our  know  ledge  concerning  this  body. 
1  Zeitschriftfiir physiologische  Chemie,  Bd.  -:-2.  S.  333,  and  1899,  Bd.  28,  S.  98.' 


BLOOD.  59 

Schmidt  prepared  solutions  of  fibrin  ferment  originally  by  adding  a  large 
excess  of  alcohol  to  blood-serum  and  allowing  the  proteids  thus  precipitated 
to  stand  under  strong  alcohol  for  a  long  time  until  they  were  thoroughly  coagu- 
lated and  rendered  nearly  insoluble  in  water.  At  the  end  of  the  proper  period 
the  coagulated  proteids  were  extracted  with  water,  and  there  was  obtained  a 
solution  which  contained  only  small  quantities  of  protcid.  It  was  found  that 
solutions  prepared  in  this  way  had  a  marked  effect  in  inducing  coagulation 
when  added  to  liquids,  such  as  hydrocele  liquid,  that  contained  fibrinogen, 
but  did  not  clot  spontaneously  or  else  clotted  very  slowly.  It  was  after- 
ward shown  that  similar  solutions  of  fibrin  ferment  are  capable  of  setting  up 
coagulation  very  readily  in  so-called  salted  plasma — that  is,  in  blood-plasma 
prevented  from  clotting  by  the  addition  of  a  certain  quantity  of  neutral  salts. 
It  was  not  possible  to  say  whether  the  coagulating  power  of  these  solutions 
was  due  to  the  small  traces  of  proteid  contained  in  them,  or  whether  the  pro- 
teid  was  merely  an  impurity.  The  general  belief  for  a  time,  however,  was 
that  the  proteids  present  were  not  the  active  agent,  and  that  there  was  in  solu- 
tion something  of  an  unknown  chemical  nature  which  acted  upon  the  fibrinogen 
after  the  manner  of  unorganized  ferments.  This  belief  was  founded  mainly 
upon  three  facts :  first,  that  the  substance  seemed  to  be  able  to  act  powerfully 
upon  fibrinogen,  although  present  in  such  minute  quantities  that  it  could  not  be 
isolated  satisfactorily  ;  second,  it  was  destroyed  by  heating  its  solutions  for  a  few 
minutes  at  60°  C. ;  and,  third,  it  did  not  seem  to  be  destroyed  in  the  reaction 
of  coagulation  which  it  set  up,  since  it  was  always  present  in  the  serum  squeezed 
out  of  the  clot.  Schmidt  proved  that  fibrin  ferment  could  not  be  obtained 
from  blood  by  the  method  described  above  if  the  blood  was  made  to  flow  im- 
mediately from  the  cut  artery  into  the  alcohol.  On  the  other  hand,  if  the  shed 
blood  was  allowed  to  stand,  the  quantity  of  fibrin  ferment  increased  up  to 
the  time  of  coagulation,  and  was  present  in  quantity  in  the  serum.  Schmidt 
believed  that  the  ferment  was  formed  in  shed  blood  from  the  disintegration 
of  the  leucocytes,  and  this  belief  was  corroborated  by  subsequent  histological 
work.  It  was  shown  in  microscopic  preparations  of  coagulated  blond  that  the 
fibrin  threads  often  radiated  from  broken-down  leucocytes — an  appearance 
that  seemed  to  indicate  that  the  leucocytes  served  as  points  of  origin  for  the 
deposition  of  the  fibrin.  When  the  blood-plates  were  discovered  a  great  deal 
of  microscopic  work  was  done  tending  to  show  that  these  bodies  also  are  con- 
nected with  coagulation  in  the  same  way  as  the  leucocytes,  and  serve  probably 
as  sources  of  fibrin  ferment.  In  microscopic  preparations  the  fibrin  threads 
were  found  to  radiate  from  masses  of  partially  disintegrated  plates  ;  and,  more- 
over, it  was  discovered  that  conditions  which  retard  or  prevent  coagulation  of 
blood  often  serve  to  preserve  the  delicate  plate-  from  disintegration.  At  the 
present  time  it  is  generally  believed  that  there  is  derived  from  the  disintegra- 
tion of  the  leucocytes  and  blood-plates  something  that  is  necessary  to  the 
coagulation  of  blood,  but  there  is  sonic  difference  of  opinion  as  to  the  nature 
of  this  substance  and  whether  it  is  identical  with  Schmidt's  fibrin  ferment. 
Pekelharing  thinks  that  the  substance  sel  free  from  the  corpuscles  and  plates 


60  AN   AMERICA*    Til  XT-BOOK    OF  PHYSIOLOGY. 

is  a  nucleo-proteid,  but  that  this  nucleo-proteid  is  not  capable  of  acting  upon 
fibrinogen  until  it  has  combined  with  the  calcium  salts  of  the  blood.  According 
to  his  view,  therefore,  fibrin  ferment,  in  Schmidt's  sense,  is  a  compound  of  cal- 
cium and  nucleo-proteid.  Lilienfeld  has  shown  by  chemical  reactions  that 
blood-plates  and  nuclei  of  leucocytes  contain  nucleo-proteid  material  which  in 
all  probability  is  liberated  in  the  blood-plasma  by  the  disintegration  of  these 
elements  after  the  blood  is  shed.  Lilienfeld  contends,  however,  that  solu- 
tions of  fibrin  ferment  prepared  by  Schmidt's  method  do  not  contain  any 
nucleo-proteid  material,  and  that,  although  the  liberation  of  nucleo-proteid 
material  is  what  starts  normal  coagulation  of  blood,  nevertheless  so-called 
fibrin  ferment  is  something  entirely  different  from  nucleo-proteid.  In  this 
point,  however,  his  results  are  contradicted  by  the  experiments  of  Pekelhar- 
ing  and  of  Halliburton,  who  both  find  that  solutions  of  fibrin  ferment  pre- 
pared by  Schmidt's  method  give  distinct  evidence  of  containing  nucleo-pro- 
teid material.  We  may  conclude,  therefore,  that  the  essential  element  of 
Schmidt's  fibrin  ferment  is  a  nucleo-proteid  compound.  The  nature  of  the 
action  of  the  ferment  on  fibrinogen  is  quite  undetermined.  As  was  mentioned 
before,  only  a  portion,  and  apparently  a  variable  portion,  of  this  fibrinogen 
appears  as  fibrin  after  clotting  is  completed.  Along  with  the  fibrin  a  new 
proteid  fibrin  globulin  makes  its  appearance  in  the  serum.  This  fact  has 
suggested  the  view  that  perhaps  the  fibrin  ferment  acts  after  the  manner  of 
the  digestive  ferments  by  causing  hydrolytic  cleavage  of  the  fibrinogen,  that 
is,  causes  the  fibrinogen  molecule  to  take  up  water  and  then  dissociate  into 
two  parts,  fibrin  and  fibrin  globulin.  Hammarsten,  however,  is  inclined  to 
believe  that  the  reaction  is  of  a  different  nature,  resembling  more  the  change 
that  occurs  in  the  heat  coagulation  of  proteids.  According  to  this  suggestion, 
the  ferment  causes  a  molecular  rearrangement  of  the  fibrinogen,  resulting  in 
the  formation  of  fibrin,  most  of  which  is  deposited  in  an  insoluble  form,  while 
a  smaller  part,  after  suffering  a  still  further  alteration,  appears  as  fibrin 
globulin. 

Intravascular  Clotting-. — Clotting  may  be  induced  within  the  blood- 
vessels  by  the  introduction  of  foreign  particles,  either  solid  or  gaseous — for 
example,  air — or  by  injuring  the  inner  coat  of  the  blood-vessels,  as  in  ligat- 
ing.  In  the  latter  case  the  area  injured  by  the  ligature  acts  as  a  foreign 
surface  and  probably  causes  the  disintegration  of  a  number  of  corpuscles. 
The  clot  in  this  case  is  confined  at  first  to  the  injured  area,  and  is  known 
a-  a  "  thrombus."  Intravascular  clotting  more  or  less  general  in  occurrence 
may  be  produced  by  injecting  into  the  circulation  such  substances  as  leucocytes 
obtained  by  macerating  lymph-glands,  extracts  of  fibrin  ferment,  solutions  of 
nucleo-albumins  of  different  kinds,  etc.  According  to  the  theory  of  coagu- 
lation adopted  above,  injections  of  these  latter  substances  ought  to  cause  coagu- 
lation very  readily,  since  the  blood  already  contains  fibrinogen,  and  needs  only 
the  presence  of  ferment  to  set  up  coagulation.  As  a  matter  of  fact,  however, 
intravascular  clotting  is  produced  with  some  difficulty  by  these  methods,  show- 
ing that  the  body  can   protect  itself  within  certain  limits  from  an  excess  of 


BLOOD.  61 

ferment  in  the  circulating  blood.  Just  how  this  is  done  is  not  positively 
known,  but  there  is  evidence  that  it  may  be  due  mainly  to  a  defensive  action 
of  the  liver.  Delezenne1  states  that  when  blood-serum  is  circulated  through 
a  liver  it  loses  its  power  of  inducing  coagulation  in  a  coagulablc  liquid,  that  is, 
probably  its  contained  fibrin  ferment  is  altered  or  destroyed.  It  seems  prob- 
able that  this  action  of  the  liver  may  be  of  importance  in  the  normal  circula- 
tion in  maintaining  the  non-coagulability  of  the  blood  in  the  living  animal. 
Moreover,  injection  of  leucocytes  sometimes  diminishes  instead  of  increasing 
the  coagulability  of  blood,  making  the  so-called  "  negative  phase "  of  the 
injection.  To  explain  this  latter  fact,  it  may  be  said  that  leucocytes  give 
rise  on  disintegration  to  a  complex  nucleo-proteid  known  as  nucleo-histon. 
Nucleo-histon  in  turn  is  said  to  be  broken  up  in  the  circulation,  with  the 
formation  of  a  second  nucleo-proteid,  leuconuclein,  that  favors  coagulation, 
and  a  proteid  body,  histon,  that  has  a  retarding  influence  on  coagulation. 
The  predominance  of  the  latter  substance  may  account  for  the  "  negative 
phase "  under  the  conditions  described. 

Why  Blood  does  not  Clot  within  the  Blood-vessels. — The  reason 
that  blood  remains  fluid  while  in  the  living  blood-vessels,  but  clots  quickly 
after  being  shed  or  after  being  brought  into  contact  with  a  foreign  substance 
in  any  way,  has  already  been  stated  in  describing  the  theories  of  coagulation, 
but  will  be  restated  here  in  more  categorical  form.  Briefly,  then,  blood 
does  not  clot  within  the  blood-vessels  because  fibrin-ferment  is  not  present  in 
sufficient  quantities  at  any  one  time.  Leucocytes  and  blood-plates  probably 
disintegrate  here  and  there  within  the  circulation,  but  the  small  amount  of 
ferment  thus  formed  is  insufficient  to  act  upon  the  blood,  and  the  ferment  is 
quickly  destroyed  or  changed,  probably  by  an  action  of  the  liver  as  stated 
above.  When  blood  is  shed,  however,  the  formed  elements  break  down  in 
mass,  as  it  were,  liberating  a  relatively  large  amount  of  nucleo-proteids, 
which,  together  with  the  calcium  salts,  produce  fibrin  from  the  fibrinogen. 

Means  of  Hastening"  or  of  Retarding-  Coagulation. — Blood  coagulates 
normally  within  a  few  minutes,  but  the  process  may  be  hastened  by  increasing 
the  extent  of  foreign  surface  with  which  it  comes  in  contact.  Tims,  moving 
the  liquid  when  in  quantity,  or  the  application  of  a  sponge  or  a  handkerchief  to 
a  wound,  will  hasten  the  onset  of  clotting.  This  is  easily  understood  when  it  is 
remembered  that  nucleo-proteids  arise  from  the  breaking  down  of  leucocytes 
and  blood-plates,  and  that  these  corpuscles  go  to  pieces  more  rapidly  when  in 
contact  with  a  dead  surface.  It  has  been  proposed  also  to  hasten  clotting  in 
case  of  hemorrhage  by  the  use  of  ferment  solutions.  Plot  sponges  or  cloths 
applied  to  a  wound  will  hasten  clotting,  probably  by  accelerating  the  formation 
of  ferment  and  the  chemical  changes  of  clotting.  Coagulation  may  be  retarded 
or  be  prevented  altogether  by  a  variety  of  means,  of  which  the  following  are 
the  most  important : 

1.  By  Cooling. — This  method  succeeds  well  only  in  blood  that  clots 
slowly — for  example,  the  blood  of  the  horse  or  the  terrapin.  Blood  from 
1  Travaux  <lr  Physiologie,  I'niversiK?  do  Montpellier,  1898. 


62  AN   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

these  animals  received  into  narrow  vessels  surrounded  by  crushed  ice  may  be 
kepi  fluid  for  an  indefinite  time.  The  blood-corpuscles  soon  sink,  so  that  this 
met  In  id  is  an  excellent  oue  for  obtaining  pure  blood-plasma.  The  cooling 
probably  prevents  clotting  by  keeping  the  corpuscles  intact. 

2.  By  the  Action  of  Neutral  Salts. — Blood  received  at  once  from  the  blood- 
vessels into  a  solution  of  such  neutral  salts  as  sodium  sulphate  or  magnesium 
sulphate,  and  well  mixed,  will  not  clot.  Jn  this  case  also  the  corpuscles  settle 
slowly,  or  they  may  be  centrifugalized,  and  specimens  of  plasma  can  be 
obtained.  For  this  purpose  horse's  or  rat's  blood  is  to  be  preferred.  Such 
plasma  is  known  as  "salted  plasma  ;"  it  is  frequently  used  in  experiments  in 
coagulation — lor  example,  in  testing  the  efficacy  of  a  given  ferment  solution. 
The  besl  -alt  to  use  is  MgS04  in  solutions  of  27  per  cent.:  1  part  by  volume 
of  this  solution  is  usually  mixed  with  4  parts  of  blood ;  if  cat's  blood  is  used  a 
smaller  amount  may  be  taken — 1  part  of  the  solution  to  9  of  blood.  Salted 
plasma  or  salted  Mood  again  clots  when  diluted  sufficiently  with  water  or  when 
ferment  solutions  are  added  to  it.  How  the  salts  prevent  coagulatiou  is  not 
definitely  known — possibly  by  preventing  the  disintegration  of  corpuscles  and 
the  formation  of  ferment,  possibly  by  altering  the  chemical  properties  of  the 
proteids. 

.1.  By  the  Action  of  Albumose  Solutions. — Certain  of  the  products  of 
proteid  digestion,  peptones  and  albumoses,  when  injected  into  the  circulation 
retard  clotting  for  a  long  time.  For  injection  into  dogs  one  uses  0.3  gram 
to  each  kilogram  of  animal.  If  the  blood  is  withdrawn  shortly  after  the 
injection,  it  will  remain  fluid  for  a  long  time.  The  peptone  solutions,  on  the 
contrary,  have  no  effect  on  the  clotting  of  blood  if  added  to  it  in  a  glass  out- 
side the  body.  This  curious  action  of  peptone  has  been  much  discussed.  In 
an  interesting  paper  by  Delezenne,  referred  to  on  the  previous  page,  two 
important  facts  are  brought  out  that  furnish  the  author  a  basis  for  a  credible 
theory  of  the  anticoagulating  effect  of  the  injections.  It  has  been  shown,  in 
the  first  place, thai  the  peptone  injections  cause  a  marked  and  rapid  destruc- 
tion of  blood  leucocytes.  Secondly,  that  if  blood  and  peptone  are  circulated 
together  through  a  living  liver  the  mixture  not  only  docs  not  clot  itself,  lmt 
will  prevent  clotting  when  added  to  freshly  drawn  blood.  The  hypothesis 
to  explain  these  facts  and  also  the  action  of  peptone  on  coagulation  is  that  the 
peptone  by  destroying  the  leucocyte-  sets  \'v<-c  nucleo-proteid  and  histon  (see 
p.  61  ):  the  former  of  these  by  forming  fibrin  ferment  would  promote  coagu- 
lation, lmt  in  passing  through  the  liver  it  is  destroyed  or  neutralized  in  some 
way.  and  the  histon  left  in  the  blood  isthe  substance  that  retards  the  clot- 
ting. It  would  be  desirable,  in  connection  with  this  hypothesis,  if  chem- 
ical proof  were  furnished  that  histon  is  present  in  the  blood  after  pepton< 
injections. 

I.  .Many  other  organic  substances  have  an  effect  similar  to  peptone  when 
injected  into  the  circulation  or  in  some  cases  when  mixed  with  shed  blood. 
For  example,  extracts  of  leech'-  head,  extract-  of  the  muscle  of  the  crayfish, 
the  serum  of  the  eel,  a  number  of  bacterial  toxins,  and  many  of  the  soluble 


BLOOD.  63 

enzymes  such  as  pepsin,  trypsin,  diastase,  etc.  The  hypothesis  u>rd  to  ex- 
plain the  action  of  peptone  may  possibly  apply  also  to  these  cases. 

5.  By  the  Action  of  Oxalate  Solutions. — If  blood  as  it  flows  from  the 
vessels  is  mixed  with  solutions  of  potassium  or  sodium  oxalate  in  proportion 
sufficient  to  make  a  total  strength  of  0.1  per  cent,  or  more  of  these  salts, 
coagulation  will  be  prevented  entirely.  Addition  of  an  excess  of  water  will 
not  produce  clotting  in  this  case,  but  solutions  of  some  soluble  calcium  salt 
will  quickly  start  the  process.  The  explanation  of  the  action  of  the  oxalate 
solutions  is  simple :  they  are  supposed  to  precipitate  the  calcium  as  insoluble 
calcium  oxalate. 

Total  Quantity  of  Blood  in  the  Body. — The  total  quantity  of  blood  in 
the  body  has  been  determined  approximately  for  man  and  a  number  of  the 
lower  animals.  The  method  used  in  such  determinations  consists  essentially 
in  first  bleeding  the  animal  as  thoroughly  as  possible  and  weighing  the  quan- 
tity of  blood  thus  obtained,  and  afterward  washing  out  the  blood-vessels  with 
water  aud  estimating  the  amount  of  haemoglobin  in  the  washings.  The  results 
are  as  follows:  Man,  7.7  per  ceut.  (y1^)  of  the  body-weight;  that  is,  a  man 
weighing  68  kilos,  has  about  5236  grams,  or  4965  c.c,  of  blood  in  his  body; 
dog,  7.7  per  cent.;  rabbit  and  cat,  5  percent.;  new-born  human  being,  5.26 
per  cent. ;  and  birds,  10  per  cent.  Moreover,  the  distribution  of  this  blood 
in  the  tissues  of  the  body  at  any  one  time  has  been  estimated  by  Ranke,1  from 
experiments  on  freshly-killed  rabbits,  as  follows : 

Spleen 0.23  per  cent. 

Brain  and  cord 1.24  "  " 

Kidneys 1.63  u 

Skin 2.10  "  " 

Intestines 6.30  ' 

Bones 8.24  "  " 

Heart,  lungs,  and  great  blood-vessels 22.76  "  " 

Resting  muscles ' 29.20  "  " 

Liver 29.30  "  « 

It  will  be  seen  from  inspection  of  this  table  that  in  the  rabbit  the  blood  of 
the  body  is  distributed  at  any  one  time  about  as  follows:  one-fourth  to  the 
heart,  lungs,  and  great  blood-vessels;  one-fourth  to  the  liver;  one-fourth  to 
the  resting  muscles;  and  one-fourth  to  the  remaining  organs. 

Regeneration  of  the  Blood  after  Hemorrhage. — A  large  portion  of  the 
entire  quantity  of  blood  in  the  body  may  be  lost  suddenly  by  hemorrhage 
without  producing  a  fatal  result.  The  extent  of  hemorrhage  thai  can  be 
recovered  from  safely  has  been  investigated  upon  a  number  of  animals. 
Although  the  results  show  more  or  less  individual  variation,  it  can  be  said 
thai  in  dogs  a  hemorrhage  of  from  2  to  3  per  cent,  of  the  body-weight8  is 
recovered  from  easily,  while  a  loss  of  1.5  per  cent.,  more  than  half  the  entire 
bl 1,  will  probably  prove  fatal.    In  eats  a  hemorrhage  of  from  'J  i<>  •"»  per 

'Taken  from  Vieronlt's  Anatoimsche,  physiologische  >ni<l  physikaltsche  Daten  "»'/  Tabellen,Jen&, 
1893. 

2  Kredericq :  Iravavx  du  LaftorotoiVe  l  University  de  LiSge),  L885,  t.  i.  p  L89. 


64  AX  AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

cent,  of  the  body-weight  is  not  usually  followed  by  a  fatal  result.  Just  what 
percentage  of  loss  can  be  borne  by  the  human  being  has  not  been  deter- 
mined, but  it  is  probable  that  a  healthy  individual  may  recover  without 
serious  difficulty  from  the  lo.-s  of  a  quantity  of  blood  amounting  to  as  much 
as  3  per  cent,  of  the  body-weight.  It  is  known  that  if  liquids  that  are  iso- 
tonic to  the  blood,  such  as  a  0.9  per  cent,  solution  of  NaCl,  are  injected  into 
the  veins  immediately  after  a  severe  hemorrhage,  recovery  will  be  more  certain  ; 
in  fact,  it  is  possible  by  this  means  to  restore  persons  after  a  hemorrhage  that 
would  otherwise  have  been  fatal.  In  addition  to  the  mechanical  effects  on 
blood  pressure  such  an  infusion  tends  to  put  into  circulation  all  the  red  cor- 
puscles. Ordinarily  the  number  of  red  corpuscles  is  greater  than  that  neces- 
sary for  a  barely  sufficient  supply  of  oxygen,  and  increasing  the  bulk  of  liquid 
in  the  vessels  after  a  severe  hemorrhage  makes  more  effective  as  oxygen-carriers 
the  remaining  red  corpuscles,  inasmuch  as  it  insures  a  more  rapid  circulation. 
If  a  hemorrhage  has  not  been  fatal,  experiments  on  lower  animals  show  that 
the  plasma  of  the  blood  is  regenerated  with  great  rapidity,  the  blood 
regaining  its  normal  volume  within  a  few  hours  in  slight  hemorrhages,  and 
in  from  twenty-four  to  forty-eight  hours  if  the  loss  of  blood  has  been 
severe ;  but  the  number  of  red  corpuscles  and  the  hemoglobin  are  regenerated 
more  slowly,  getting  back  to  normal  only  after  a  number  of  days  or  after 
several  weeks. 

Blood-transfusion. — Shortly  after  the  discovery  of  the  circulation  of  the 
blood  (Harvey,  1628),  the  operation  was  introduced  of  transfusing  blood  from 
one  individual  to  another  or  from  some  of  the  lower  animals  to  man.  Ex- 
travagant hopes  were  held  as  to  the  value  of  such  transfusion  not  only  as  a 
means  of  replacing  the  blood  lost  by  hemorrhage,  but  also  as  a  cure  for  various 
infirmities  and  diseases.  Then  and  subsequently,  fatal  as  well  as  successful 
results  followed  the  operation.  It  is  now  known  to  be  a  dangerous  under- 
taking, mainly  for  two  reasons:  first,  the  strange  blood,  whether  transfused 
directly  or  after  defibrination,  is  liable  to  contain  a  quantity  of  fibrin  ferment 
sufficient  to  cause  intravascular  clotting;  secondly,  the  serum  of  one  animal 
may  be  toxic  to  another  or  cause  a  destruction  of  its  blood-corpuscles.  Owing 
to  this  globulicidal  and  toxic  action,  which  has  previously  been  referred  to 
(p.  36),  the  injection  of  foreign  blood  is  likely  to  be  directly  injurious  instead 
of  beneficial.  In  cases  of  loss  of  blood  from  severe  hemorrhage,  therefore,  it 
is  far  safer  to  inject  a  neutral  liquid,  such  as  the  so-called  "  physiological  salt- 
solution  " — a  solution  of  NaCl  of  such  a  strength  (0.9  per  cent.)  as  to  be  iso- 
tonic with  the  blood-serum.  The  volume  of  the  circulating  liquid  is  thereby 
augmented,  and  all  the  red  corpuscles  are  made  more  efficient  as  oxygen- 
carriers,  partly  owing  to  the  fact  that  the  bulk  and  velocity  of  the  circulation 
are  increased,  and  partly  because  the  corpuscles  are  kept  from  stagnation  in  the 
capillary  areas. 


DIFFUSION  AND   OSMOSIS.  65 

Some  Preliminary  Considerations  upon  the  Processes  of  Diffusion  and 
Osmosis,  and  their  Importance  in  the  Nutritive  Exchanges  of  the 
Body. 

In  recent  years  the  physical  conceptions  of  the  nature  of  the  processes  of  diffusion  and 
osmosis  have  changed  considerably.  As  these  newer  conceptions  are  entering  largely 
into  current  medical  literature,  it  seems  advisable  to  give  a  brief  description  of  them 
for  the  use  of  those  students  of  physiology  who  may  be  unacquainted  with  the  modern 
nomenclature.  The  very  limited  space  that  can  be  devoted  to  the  subject  forbids  any- 
thing more  than  a  condensed  elementary  presentation.  For  fuller  information  reference 
must  be  made  to  special  treatises.1 

Diffusion,  Dialysis,  and  Osmosis. — When  two  gases  are  brought  into  contact  a  homo- 
geneous mixture  of  the  two  is  soon  obtained.  This  interpenetration  of  the  gases  is 
spoken  of  as  diffusion,  and  it  is  due  to  the  continual  movements  of  the  gaseous 
molecules  to  and  fro  within  the  limits  of  the  confining  space.  So  also  when  two  mis- 
cible  liquids  or  solutions  are  brought  into  contact  a  diffusion  occurs  for  the  same  reason, 
the  movements  of  the  molecules  finally  effecting  a  homogeneous  mixture.  If  the  two 
liquids  happen  to  be  separated  by  a  membrane,  diffusion  will  still  occur,  provided  the 
membrane  is  permeable  to  the  liquid  molecules,  and  in  time  the  liquids  on  the  two  sides 
will  be  mixtures  having  a  uniform  composition.  Not  only  water  molecules,  but  the  mole- 
cules of  many  substances  in  solution,  such  as  sugar,  may  pass  to  and  fro  through  mem- 
branes, so  that  two  liquids  separated  from  each  other  by  an  intervening  membrane  and 
originally  unlike  in  composition  may  finally,  by  the  act  of  diffusion,  come  to  have  the  same 
composition.  Diffusion  of  this  kind  through  a  membrane  is  frequently  spoken  of  as 
dialysis  or  osmosis.  In  the  body  we  deal  with  aqueous  solutions  of  various  substances 
that  are  separated  from  each  other  by  living  membranes,  such  as  the  walls  of  the  blood- 
capillaries  or  of  the  alimentary  canal,  and  the  laws  of  diffusion  through  membranes  are 
of  immediate  importance  in  explaining  the  passage  of  water  and  dissolved  substances 
through  these  living  septa.  In  aqueous  solutions  such  as  we  have  in  the  body  we  must 
take  into  account  the  movements  of  the  molecules  of  the  solvent,  water,  as  well  as  of  the 
substances  dissolved.  These  latter  may  have  different  degrees  of  diffusibility  as  compared 
with  one  another  or  with  the  water  molecules,  and  it  frequently  happens  that  a  membrane 
that  is  permeable  to  water  molecules  is  less  permeable  or  even  impermeable  to  the  mole- 
cules of  the  substances  in  solution.  F'or  this  reason  the  diffusion  stream  of  water  and  of 
the  dissolved  substances  may  be  differentiated,  as  it  were,  to  a  greater  or  less  extent.  In 
recent  years  it  seems  to  have  become  customary  to  limit  the  term  osmosis  to  the  stream 
of  water  molecules  passing  through  a  membrane,  while  the  term  dialysis,  or  diffusion,  is 
applied  to  the  passage  of  the  molecules  of  the  substances  in  solution.  The  osmotic 
stream  of  water  under  varying  conditions  is  especially  important,  and  in  connection 
with  this  process  it  is  necessary  to  define  the  term  osmotic  pressure  as  applied  to 
solutions. 

Osmotic  Pressure. — If  we  imagine  two  masses  of  water  separated  by  a  permeable 
membrane,  we  can  readily  understand  that  as  many  water  molecules  will  pass  through 
from  one  side  as  from  the  other;  the  two  streams  in  fact  will  neutralize  each  other,  and 
the  volumes  of  the  two  masses  of  water  will  remain  unchanged.  The  movement  of  the 
water  molecules  in  this  case  is  not  actually  observed,  but  it  is  assumed  to  take  place  on 
the  theory  that  the  liquid  molecules  are  continually  in  motion  and  thai  the  membrane, 
being  permeable,  offers  no  obstacle  to  their  movements.  If,  now.  on  one  side  of  the 
membrane  we  place  a  solution  of  some  crystalloid  substance,  such  as  common  salt,  and 
on  the  other  side  pure  water,  then  it  will  he  found  that  an  excess  of  water  will  pass  from 

1  Consult:  II. C.  Jones,  The  Theory  of  Electrolytic  Dissociation,  1900;  "  Diffusion,  Osmosis, and 

Filtration,"  by  E.  W.  Reid,  in  Schlifer's  Test-book  of  Physiology,  1898;  Solution  and  Electrolysis, 
by  W.  C  I).  Whetham,  Cambridge  Natural  Science  Manuals.  1895. 
Vol.  I.— 5 


66  l.V    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

the  water  side  to  the  Bide  containing  the  solution.  In  the  older  terminology  it 
was  said  thai  the  sail  attracted  this  water,  but  in  the  newer  theories  the  same  fact  is 
expressed  by  saying  that  the  salt  in  solution  exerts  a  certain  osmotic  pressure,  in  eonse- 
quence  of  which  more  water  flows  from  the  water  side  to  the  side  of  the  solution  than  in 
the  reverse  direction.  A-  a  matter  of  experiment  it  is  found  that  the  osmotic  pressure 
varies  with  the  amount  of  the  substance  in  solution.  If  in  experiments  of  this  kind  a 
semi-permeable  membrane  is  chosen — that  is,  a  membrane  that  is  permeable  to  the  water 
molecules,  hut  not  to  the  molecules  of  the  substance  in  solution— the  stream  of  water  to 
i lie  Bide  of  the  crystalloid  will  continue  until  the  hydrostatic  pressure  on  this  side 
reaches  a  certain  point,  and  the  hydrostatic  pressure  thus  caused  may  he  taken  as  a 
measure  of  the  osmotic  pressure  exerted  by  the  substance  in  solution.  Under  these  con- 
dition- it  can  he  shown  that  the  osmotic  pressure  is  proportional  to  the  concentration  of 
the  solution,  or,  in  other  words,  to  the  Dumber  of  molecules  and  ions  of  the  crystalloid  in 
solution.  As  a  matter  of  fact  it  is  difficult,  if  not  impossible,  to  construct  membranes 
that  are  truly  semi-permeable;  most  of  the  membranes  that  we  have  to  use  in  practice 
are  only  approximately  semi-permeable— that  is,  while  they  are  readily  permeable  to 
water  molecule-,  they  arc  also  permeable,  although  with  more  or  less  difficulty,  to  the 
substances  in  solution.  In  such  cases  we  get  an  osmotic  stream  of  water  to  the  side  of  the 
dissolved  crystalloid,  but  at  the  same  time  the  molecules  of  the  latter  pass  to  some  extent 
through  the  membrane,  by  diffusion,  to  the  water  side.  In  course  of  time,  therefore,  the 
dissolved  crystalloid  will  he  equally  distributed  on  the  two  sides  of  the  membrane,  the 
osmotic  pressure  on  both  sides  will  become  equal,  and  osmosis  of  the  water  will  cease 
to  be  apparent,  since  it  will  be  equal  in  the  two  directions.  All  substances  iu  solution  are 
capable  of  exerting  osmotic  pressure,  and  the  important  discovery  has  been  made  that 
the  osmotic  pressure,  measured  in  terms  of  atmospheres  or  the  pressure  of  a  column  of 
water  or  mercury,  is  equal  to  the  gas  pressure  that  would  be  exerted  by  a  number  of 
molecules  of  gas  equal  to  that  of  the  crystalloid  in  solution,  if  confined  within  the  same 
-pace  ami  kept  at  the  same  temperature.  A  perfectly  satisfactory  explanation  of  the 
nature  of  osmotic  pressure  has  not  been  furnished.  We  must  be  content  to  use  the  term 
to  express  the  fact  described.  A  comparatively  simple  explanation,  however,  has  been 
suggested,  which  has  the  great  merit  of  referring  the  whole  phenomenon  to  the  molec- 
ular movements  of  the  solvent  and  of  the  substance  dissolved — that  is,  to  the  same 
ultimate  cause  that  brings  about  the  entire  process  of  diffusion  in  liquids.  The  nature 
of  this  explanation  may  he  understood  from  a  simple  illustration.  Suppose  that  we 
have  a  solution  of  cane-sugar  separated  from  a  mass  of  water  by  a  semi-permeable  mem- 
brant — that  is,  in  this  case  a  membrane  permeable  to  the  water  molecules  but  not  to  the 
sugar  molecules.  Under  these  conditions  the  stream  of  water  from  the  two  sides 
will  lie  unequal,  because  on  the  one  side  we  have  water  molecules  moving  against 
the  membrane  in  what  we  may  call  normal  numbers,  while  on  the  other  side  both  water 
and  BUgar  molecules  may  be  considered  as  striking  against  the  membrane.  On  this  side 
the  sugar  molecules  screen  the  membrane,  as  it  were,  from  contact  with  a  certain  num- 
ber of  water  molecules,  and  the  result  follows  that  in  a  given  unit  of  time  fewer  mole- 
cule- of  water  will  penetrate  the  membrane  from  this  side  than  from  the  other;  or,  to 
put  it  in  another  way,  the  osmotic  stream  of  water  from  the  unscreened  water  side  to  the 
sugar  side  will  be  greater  than  in  the  reverse  direction.  Upon  this  hypothesis  one 
can  readily  see  why  the  osmotic  pressure  should  be  proportional  to  the  number  of  mole- 
cules  of  the  crystalloid  in  the  solution — that  is,  to  the  concentration  of  the  solution.  It 
i-  a  matter  of  great  importance  to  measure  the  osmotic  pressures  of  various  solutions. 
A-  was  -tated  above,  this  mea-uremeiit  could  lie  made  easily  for  any  solution  provided 
a  really  -emi-permeable  membrane  could  be  constructed.  As  a  matter  of  experience, 
however,  it  is  possible  to  make  stub  membranes  in  only  a  few  cases,  and  in  these  cases 
perhaps  the  semi-permeability  is  only  approximately  complete.     In  actual  experiments 

other  methods  must  1 mployed,  and  a  brief  statement  of  a  theoretical  and  a  practical 

method  of  arriving  at  the  value  of  osmotic  pressures  may  be  of  service  in  further  illus- 


DIFFUSION  AND   OSMOSIS.  67 

trating  the  meaning  of  the  term.  Before  stating  these  met  Ik  ids  it  hecomes  necessary  to 
define  two  terms,  namely,  electrolytes  and  gram-molecular  solutions,  that  are  much  used 
in  this  connection. 

Electrolysis. — The  molecules  of  many  substances  when  brought  into  a  state  of  solution 
are  believed  to  be  dissociated  into  two  or  more  parts,  known  as  ions.  The  complete- 
ness of  the  dissociation  varies  with  the  substance  used,  and  for  any  one  substance  with 
the  degree  of  dilution.  Roughly  speaking,  the  greater  the  dilution  the  more  nearly 
complete  is  the  dissociation.  The  ions  liberated  by  this  act  of  dissociation  are 
charged  with  electricity,  ar.d  when  an  electrical  current  is  led  into  such  a  solution  it  is 
conducted  through  the  solution  by  the  movements  of  the  ions.  The  molecules  of  per- 
fectly pure  water  undergo  practically  no  dissociation,  and  water  therefore  does  not  appre- 
ciably conduct  the  electrical  current.  If  some  NaCl  is  dissolved  in  water,  a  certain  num- 
ber of  its  molecules  become  dissociated  into  a  Na  ion  charged  positively  with  electricity 
and  a  CI  ion  charged  negatively,  and  the  solution  becomes  a  conductor  of  the  electrical 
current.  Substances  that  exhibit  this  property  of  dissociation  are  known  as  electrolytes, 
to  distinguish  them  from  other  soluble  substances,  such  as  sugar,  that  do  not  dissociate 
in  solution  and  therefore  do  not  conduct  the  electrical  current.  Speaking  generally,  it 
may  be  said  that  all  salts,  bases,  and  acids  belong  to  the  group  of  electrolytes.  The  con- 
ception of  electrolytes  is  very  important  for  the  reason  that  the  act  of  dissociation 
obviously  increases  the  number  of  particles  moving  in  the  solution  and  thereby  increases 
the  osmotic  pressure,  since  it  has  been  found  experimentally  that,  so  far  as  osmotic 
pressures  are  concerned,  an  ion  plays  the  same  part  as  a  molecule.  It  follows,  there- 
fore, that  the  osmotic  pressure  of  any  given  electrolyte  in  solution  will  be  increased  in 
proportion  to  the  degree  to  which  it  is  dissociated.  As  the  liquids  of  the  body  contain 
electrolytes  in  solution  it  becomes  necessary  in  estimating  their  osmotic  pressure  to  take 
this  fact  into  consideration. 

Gram-molecular  Solutions. — The  concentration  of  a  given  substance  in  solution  may 
be  stated  by  the  usual  method  of  percentages,  but  from  the  standpoint  of  osmotic  press- 
ure a  more  convenient  method  is  the  use  of  the  unit  known  as  a  gram-molecular 
solution.  A  gram-molecule  of  any  substance  is  a  quantity  in  grams  of  the  substance 
equal  to  its  molecular  weight,  while  a  gram-molecular  solution  is  one  containing  a  gram- 
molecule  of  the  substance  to  a  liter  of  the  solution.  Thus  a  gram-molecular  solution  of 
sodium  chloride  is  one  containing  58.5  grams  (Na  23,  CI  35.5)  of  the  salt  to  a  liter,  while  a 
gram-molecular  solution  of  cane-sugar  contains  342.1  grains  (C12H22On)  to  a  liter.  Sim- 
ilarly a  gram-molecule  of  H  is  2  grains  by  weight  of  this  gas,  and  if  this  weight  of  II  were 
compressed  to  the  volume  of  a  liter  it  would  be  comparable  to  a  gram-molecular  solution. 
Since  the  weight  of  a  molecule  of  II  is  to  the  weight  of  a  molecule  of  cane-sugar  as  2  is 
to  342.1,  it  follows  that  a  liter  containing  2  grams  of  II  contains  the  same  number  of 
molecules  of  H  in  it  as  a  liter  of  solution  containing  342.1  grains  of  sugar  has  of  sugar 
molecules.  Since  it  is  known  that  a  molecule  in  solution  exerts  an  osmotic  pressure 
that  is  exactly  equal  to  the  gas-pressure  exerted  by  a  gas  molecule  moving  in  the  same 
space  and  at  the  same  temperature,  we  are  justified  in  saying  that  the  osmotic  pressure 
of  a  ^ram-molecular  solution  of  cane-sugar,  or  of  any  other  substance  that  is  not  an 
electrolyte,  is  equal  to  the  gas-pressure  of  2  grams  of  II  when  compressed  to  the  volume 
of  1  liter.  This  fact  gives  a  means  of  calculating  the  osmotic  pressure  of  solutions  in 
certain  cases  according  to  the  following  method  : 

Calculation  of  flu'  Osmotic  I'rcssurr  of  Solution.-!.  -To  illustrate  this  method  we  may 
take  a  simple  problem  such  as  the  determination  of  the  osmotic  pressure  of  a  1  per  cent. 
solution  of  cane-sugar.  One  gram  of  II  at  atmospheric  pressure  occupies  a  volume  of 
11.16  liters  ;  2  grains  of  II,  therefore,  under  the  same  conditions  will  occupy  a  volume  of 
22.32  liters.  A  gram-molecule  of  H— that  is,  2  grams  of  II — when  broughl  to  the  volume 
ofl  liter  will  exert  a  gas-pressure  equal  to  that  of  22.32  liters  compressed  to  I  liter — that 
is,  a  pressure  of  22.32  atmospheres.  A  gram-molecular  solution  of  cane-sugar,  since  it  con- 
tains the  same  number  of  molecules  in  a  liter,  must  therefore  exert  an  osmotic  pressure 


68  AN  AMERICAN    TEXT-HOOK    OF  PHYSIOLOGY. 

equal  to  -~2.'-','2  atmospheres.     A  1  per  cent,  solution  of  cane  sugar  contains,  however, 
only  10  grams  of  sugar  to  a  liter,  hence  the  osmotic  pressure  of  the  sugar  in  such  a  solu- 
tion  will  be     ■     -   of  22.32  atmospheres,  or  0.G5  of  an  atmosphere,  which  in  terms  of  a 
342.J 

column  of  mercury  would  give  760  X  0.65  =  494  mm.  This  figure  expresses  the 
osmotic  pressure  of  a  1  per  cent,  solution  of  cam-sugar  when  dialyzed  against  pure 
water  through  a  membrane  impermeable  to  the  sugar  molecules.  In  such  an  experi- 
ment water  would  pass  to  the  sugar  side  until  the  hydrostatic  pressure  on  this  side  was 
increased  by  an  amount  equal  to  the  pressure  of  a  column  of  mercury  494  mm.  high. 
Certain  additional  calculations  that  it  is  necessary  to  make  for  the  temperature  of  the 
solution  need  not  be  specified  in  this  connection.  If,  however,  we  wished  to  apply  this 
method  to  the  calculation  of  the  osmotic  pressure  of  a  given  solution  of  an  electrolyte, 
it  would  be  necessary  first  to  ascertain  the  degree  of  dissociation  of  the  electrolyte  into 
its  ions,  since,  as  was  said  above,  dissociation  increases  the  number  of  parts  in  solu- 
tion and  to  the  same  extent  increases  osmotic  pressure.  In  the  body  the  liquids  that 
concern  us  contain  a  variety  of  substances  in  solution,  electrolytes  as  well  as  non- 
electrolytes.  In  order,  therefore,  to  calculate  the  osmotic  pressure  of  such  complex  solu- 
tions it  would  be  necessary  to  ascertain  the  amount  of  each  substance  present,  and,  in 
the  case  of  electrolytes,  the  degree  of  dissociation.  Under  experimental  conditions  such 
a  calculation  is  practically  impossible,  and  recourse  must  be  had  to  other  methods.  One 
of  the  simplest  and  most  easily  applied  of  these  methods  is  the  determination  of  the 
freezing-point  of  the  solution. 

Determination  of  Os?notic  Pressure  by  Means  of  the  Freezing-point. — This  method 
depends  upon  the  fact  that  the  freezing-point  of  water  is  lowered  by  substances  in  solu- 
tion, and  it  has  been  discovered  that  the  amount  of  lowering  is  proportional  to  the  number 
of  parts  (molecules  and  ions)  present  in  the  solution.  Since  the  osmotic  pressure  is 
also  proportional  to  the  number  of  parts  in  solution,  it  is  convenient  to  take  the  lowering 
of  the  freezing-point  of  a  solution  as  an  index  or  measure  of  its  osmotic  pressure.  In 
practice  a  simple  apparatus  (Beckmann's  apparatus)  is  used,  consisting  essentially  of  a 
very  delicate  and  adjustable  differential  thermometer.  By  means  of  this  instrument 
the  freezing-point  of  pure  water  is  first  ascertained  upon  the  empirical  scale  of  the 
thermometer.  The  freezing-point  of  the  solution  under  examination  is  then  determined, 
and  the  number  of  degrees  or  fractions  of  a  degree  by  which  its  freezing-point  is  lower 
than  that  of  pure  water  is  noted.  The  lowering  of  the  freezing-point  in  degrees  centi- 
grade is  expressed  usually  by  the  symbol  A.  For  example,  mammalian  blood-serum 
gives  A  =  0.56°  C.  A  0.95  per  cent,  solution  of  XaCl  gives  the  same  A  ;  hence  the  two 
solutions  exert  the  same  osmotic  pressure,  or,  to  put  it  in  another  way,  a  0.95  per  cent. 
solution  of  NaCl  is  isotonic  or  isosmotic  with  mammalian  serum.  The  A  of  any  given 
solution  may  be  exprc-sed  in  terms  of  a  gram-molecular  solution  by  dividing  it  by  the 
constant  1.87,  since  a  gram-molecular  solution  of  a  non-electrolyte  is  known  to  lower 
the  freezing  point  1.87°  C.     Thus  if  blood-serum  gives  A  =  0.56°  C,  its  concentration  in 

0.56 
terms  of  a  gram-molecular  solution  will  be  T~o-,  or  0.3.     In  other  words,  blood-serum 

has  0.3  of  the  osmotic  pressure  exerted  by  a  gram-molecular  solution  of  a  non-electro- 
lyte—that is,  22.32  x  0.3,  or  6.696  atmospheres. 

Remarks  upon  tin  Application  of  the  Foregoing  Fact*  in  Physiology. — In  the  body  water 
and  substances  in  solution  are  continually  passing  through  membranes,  for  example,  in 
the  production  of  lymph,  in  the  absorption  of  water  and  digested  food-stuff's  from  the 
alimentary  canal,  in  the  nutritive  exchanges  between  the  tissue-elements  and  the  blood 
or  lymph,  in  the  production  of  the  various  secretion-;,  and  so  on.  In  these  cases  it  is  a 
matter  of  the  greatest  difficulty  to  give  a  satisfactory  explanation  of  the  forces  control- 
ling the  flow  to  and  fro  of  the  water  and  dissolved  substances;  but  there  can  be  little 
doubt  that  in  all  of  them  the  physical  forces  of  filtration,  diffusion,  and  osmosis  take  an 
important  part.     Whatever  can  be  learned  therefore  concerning  these  processes  must  iu 


DIFFUSION  AND   OSMOSIS.  69 

the  end  have  an  important  bearing  upon  the  explanation  of  the  nutritive  exchanges 
between  the  blood  and  tissues.  Some  additional  facts  may  be  mentioned  to  indicate 
the  applications  that  are  made  of  these  processes  in  explaining  physiological  phenomena. 

Osmotic  Pressure  of  Proteids. — The  osmotic  pressure  exerted  by  crystalloids,  such  as 
the  ordinary  soluble  salts,  is,  as  we  have  seen,  very  considerable,  but  the  ready  diffusi- 
bility  of  most  of  these  salts  through  animal  membranes  limits  very  materially  their  influ- 
ence upon  the  flow  of  water  in  the  body.  Thus  if  we  should  inject  a  strong  solution  of 
common  salt  directly  into  the  blood-vessels,  the  first  effect  would  be  the  setting  up  of  an 
osmotic  stream  from  the  tissues  to  the  blood  and  the  production  of  a  condition  of  hydremic 
plethora  within  the  blood-vessels.  The  salt,  however,  would  soon  diffuse  out  into  the  tis- 
sues, and  to  the  degree  that  this  occurred  its  effect  in  diluting  the  blood  would  tend  to  dimin- 
ish because  the  part  of  the  salt  that  got  into  the  extra-vascular  lymph-spaces  would  now 
exert  an  osmotic  pressure  in  the  opposite  direction,  drawing  water  from  the  blood.  This 
fact,  together  with  the  further  fact  that  an  excess  of  salts  in  the  body  is  soon  removed  by 
the  excreting  organs,  gives  to  such  substances  a  smaller  influence  in  directing  the  water 
stream  than  would  at  first  be  supposed  when  the  intensity  of  their  osmotic  action  is  con- 
sidered. In  addition  to  the  crystalloids  the  liquids  of  our  bodies  contain  also  a  certaiu 
amount  of  proteid,  the  blood,  especially,  containing  over  6  per  cent,  of  this  substance.  It 
has  been  generally  assumed  that  proteids  in  solution  exert  little  or  no  osmotic  pressure, 
but  Starling  1  and  others  have  claimed,  on  the  contrary,  that  proteids  in  solution  exert  a 
distinct  although  small  osmotic  pressure,  and  it  is  probable  that  this  fact  is  of  special 
importance  in  absorption  because  the  proteids  do  not  diffuse  or  diffuse  with  great 
difficulty,  and  their  effect  remains  therefore,  so  to  speak,  as  a  permanent  factor.  Accord- 
ing to  Starling,  the  osmotic  pressure  exerted  by  the  proteids  of  serum  is  equal  to  about 
30  mm.  of  mercury.  That  the  osmotic  pressure  of  the  serum  proteids  is  so  small  is  not 
surprising  if  we  remember  the  very  high  molecular  weight  of  this  substance.  In  serum 
the  proteids  are  present  in  a  concentration  of  about  7  per  cent.,  but  owing  to  their  large 
molecular  weight  comparatively  few  proteid  molecules  are  present  in  a  solution  of  this 
concentration ;  and  assuming  that  the  dissolved  proteid  follows  the  laws  discovered  for 
crystalloids  its  osmotic  pressure  would  depend  upon  the  number  of  molecules  in  solu- 
tion. By  means  of  this  weak  but  constant  osmotic  pressure  of  the  indiffusible  proteid 
it  is  possible  to  explain  the  fact  that  an  isotonic  or  even  a  hypertonic  solution  of  diffus- 
ible crystalloid  may  be  completely  absorbed  by  the  blood  from  the  peritoneal  cavity. 

Isotonic,  Hypertonic,  and  Hypotonic  Solutions. — In  physiology  the  osmotic  pressures 
exerted  by  various  solutions  are  compared  usually  with  that  of  the  blood-serum.  In  this 
sense  an  isotonic  or  isosmotic  solution  is  one  having  an  osmotic  pressure  equal  to  that 
of  serum,  a  hypertonic  or  hyperosmotic  solution  is  one  whose  osmotic  pressure  exceeds 
that  of  serum,  and  a  hypotonic  or  hyposmotic  solution  is  one  whose  osmotic  pressure  is 
less  than  that  of  serum. 

Diffusion,  or  Dialysis,  of  Soluble  Constituents. — If  two  liquids  of  unequal  concentration 
in  a  given  constituent  are  separated  by  a  membrane  entirely  permeable  to  the  dissolved 
molecules  of  the  substance,  a  greater  number  of  these  molecules  will  pass  over  from  the 
more  concentrated  to  the  less  concentrated  side,  and  in  time  the  composition  will  be  the 
same  on  the  two  sides  of  the  membrane.  Diffusion  of  soluble  constituents  continually  takes 
place,  therefore,  from  the  points  of  greater  concentration  to  those  ofless,  and  this  may  bap- 
pen  quite  independently  of  the  direction  of  the  osmotic  stream  of  water.  I  f.  for  instance,  a 
0.9  per  cent,  solution  of  sodium  chloride  is  injected  into  the  peritoneal  cavity,  it  will  enter 
into  diffusion  relations  with  the  blood  in  the  blood-vessels;  its  concentration  in  sodium 
chloride  being  greater  than  that  of  the  blood,  the  excess  will  tend  to  pass  into  the  blood, 
while  sodium  carbonate,  urea,  sugar,  and  other  soluble  crystalloidal  substances  will  pass 
from  the  blood  into  the  salt  solution  in  the  peritoneal  cavity.  Through  the  action  of 
this  process  of  diffusion  we  can  understand  how  certain  constituents  of  the  blood  may  pass 

1  Journal  of  Physiology,  L899,  vol.  24,  |>.  .".IT. 


70  AN   AMERICAN    TEXT- HOOK    OF  PHYSIOLOGY. 

to  the  tissues  of  various  glands  in  amounts  greater  than  could  be  explained  if  we  sup- 
posed that  the  lymph  of  these  tissues  was  derived  solely  by  filtration  from  the  blood- 
plasma.  (See  p.  ~'l  for  an  illustration.)  Another  important  conception  in  this  con- 
nection is  the  possibility  that  the  capillary  walls  may  be  permeable  in  different  degrees 
to  the  various  soluble  constituents  of  the  blood,  and  furthermore  the  possibility  that 
the  permeability  of  the  capillary  walls  may  vary  in  different  organs.  With  regard  to 
the  first  possibility  it  has  been  shown  by  Roth  '  that  the  blood-capillaries  are  more  per- 
meable to  the  urea  molecules  than  to  sugar  or  NaCl.  With  the  aid  of  these  facts  it  is 
possible  to  explain  in  Large  measure  the  transportation  of  material  from  the  blood  to 
the  tissues,  and  vice  versa.  For  example,  to  follow  a  line  of  reasoning  used  by  Roth,  we 
may  suppose  that  the  functional  activity  of  the  tissue-elements  is  attended  by  a  con- 
sumption of  material  which  in  turn  is  made  good  by  the  dissolved  molecules  in  the 
tissue-lymph.  The  concentration  of  the  latter  is  thereby  lowered,  and  in  consequence  a 
diffusion  stream  of  these  substance-  is  set  up  with  the  more  concentrated  blood.  In  this 
way,  by  diffusion,  a  constant  supply  of  dissolved  material  is  kept  in  motion  from  the 
blood  to  the  tissue-elements.  On  the  other  hand,  the  functional  activity  of  the  tissue- 
elements  is  accompanied  by  a  breaking  down  of  the  complex  proteid  molecule  with  the 
formation  of  simpler,  more  stable  molecules  of  crystalloid  character,  such  as  the  sul- 
phates, phosphates,  and  urea  or  some  precursor  of  urea.  As  these  bodies  pass  into  the 
tissue-lymph  they  tend  to  increase  its  molecular  concentration,  and  thus  by  the  greater 
osmotic  pressure  which  they  exert  serve  to  attract  water  from  the  blood  to  the  lymph, 
forming  one  efficient  factor  in  the  production  of  lymph.  On  the  other  hand,  as  these 
substances  accumulate  in  the  lymph  to  a  concentration  greater  than  that  possessed  by 
the  same  substances  in  the  blood,  they  will  diffuse  toward  the  blood.  By  this  means  the 
waste-products  of  activity  are  drawn  off  to  the  blood,  from  which  in  turn  they  are 
removed  by  the  action  of  the  excretory  organs. 

Diffusion  of  Proteids. — This  simple  explanation  on  purely  physical  grounds  of  the 
flow  of  material  between  the  blood  and  the  tissues  can  only  be  applied,  however,  at 
present  to  the  diffusible  crystalloids,  such  as  the  salts,  urea,  and  sugar.  The  proteids  of 
the  blood,  which  are  supposed  to  be  so  important  for  the  nutrition  of  the  tissues,  are  prac- 
tically indiffusible,  so  far  as  we  know.  It  is  difficult  to  explain  their  passage  from  the 
blood  through  the  capillary  walls  into  the  lymph.  Provisionally  it  may  be  assumed 
that  this  passage  is  due  to  filtration.  The  blood-plasma  in  the  capillaries  is  under 
a  slightly  higher  pressure  than  the  lymph  of  the  tissues,  and  this  higher  pressure  tends 
t"  Mpieeze  the  blood-constituents,  including  the  proteid,  through  the  capillary  walls. 
Tin-  explanation,  however,  cannot  be  said  to  be  satisfactory,  and  in  this  respect  the 
purely  physical  theory  of  lymph-formation  waits  upon  a  clearer  knowledge  of  the  nature 
of  the  nutritive  proteids  and  their  relations  to  the  capillary  walls. 


LYMPH. 

LYMPH  is  a  colorless  liquid  found  in  the  lymph-vessels  as  well  as  in  the 
extravascular  spaces  of  the  body.  All  the  tissue-elements,  in  fact,  may  be 
regarded  as  being  bathed  in  lymph.  To  understand  its  occurrence  in  the  body 
one  has  only  to  hear  in  mind  its  method  of  origin  from  the  blood.  Throughout 
the  entire  body  there  is  a  rich  supply  of  blood-vessels  penetrating  every  tissue 
with  the  exception  of  the  epidermis  and  some  epidermal  structures,  as  the  nails 
and  the  hair.  The  plasma  of  the  blood,  by  the  action  of  physical  or  chemical 
processes,  the  details  <d*  which  are  not  vet  entirely  understood,  makes  its  way 
through  the  thin  walls  id'  the  capillaries,  and  is  thus  brought  into  immediate 

1  Archiv  fur  Physiohgie,  1899,  8.  416. 


LYMPH.  71 

contact  with  the  tissues,  to  which  it  brings  the  nourishment  and  oxygen  of 
the  blood  and  from  which  it  removes  the  waste-products  of  metabolism.  This 
extravascular  lymph  is  collected  into  small  capillary  spaces  that  in  turn  open 
into  definite  lymphatic  vessels.  These  vessels  unite  to  larger  and  larger 
trunks,  forming  eventually  one  main  trunk,  the  thoracic  or  left  lymphatic 
duct,  and  a  second  smaller  right  lymphatic  duct,  which  open  into  the  blood- 
vessels, each  on  its  own  side,  at  the  junction  of  the  subclavian  and  internal 
jugular  veins.  While  the  supply  of  lymph  in  the  lymph-vessels  may  be  consid- 
ered as  being  derived  ultimately  entirely  from  the  blood-plasma,  it  is  well  to  bear 
in  mind  that  at  any  given  moment  this  supply  may  be  altered  by  direct  inter- 
change with  the  plasma  on  one  side  and  the  extravascular  lymph  permeating  the 
tissue-elements  on  the  other.  The  intravascular  lymph  may  be  augmented. 
for  example,  by  a  flow  of  water  from  the  plasma  into  the  lymph-spaces,  or 
by  a  flow  from  the  tissue-elements  into  the  lymph-spaces  that  surround  them. 
The  lymph  movement  is  from  the  tissues  to  the  veins,  and  the  flow  is  main- 
tained chiefly  by  the  difference  in  pressure  between  the  lymph  at  its  origin  in 
the  tissues  and  in  the  large  tymphatic  vessels.  The  continual  formation  of 
lymph  in  the  tissues  leads  to  the  development  of  a  relatively  high  pressure  in 
the  lymph  capillaries,  and  as  a  result  of  this  the  lymph  is  forced  toward  the 
point  of  lowest  pressure — namely,  the  points  of  junction  of  the  large  lymph- 
ducts  with  the  venous  system.  A  fuller  discussion  of  the  factors  concerned  in 
the  movement  of  lymph  will  be  found  in  the  section  on  Circulation.  As  would 
be  inferred  from  its  origin,  the  composition  of  lymph  is  essentially  the  same  as 
that  of  blood-plasma.  Lymph  contains  the  three  blood-proteids,  the  extractives 
(urea,  fat,  lecithin,  cholesteriu,  sugar),  and  inorganic  salts.  The  salts  are  found 
in  the  same  proportions  as  in  the  plasma;  the  proteids  are  less  in  amount,  espe- 
cially the  fibrinogen.  Lymph  coagulates,  but  does  so  more  slowly  and  less 
firmly  than  the  blood.  Histologically,  lymph  consists  of  a  colorless  liquid  con- 
taining a  number  of  leucocytes,  and  after  meals  a  number  of  minute  fat-drop- 
lets;  red  blood-corpuscles  occur  only  accidentally,  and  blood-plates,  according 
to  most  accounts,  are  likewise  normally  absent. 

Formation  of  Lymph. — The  careful  researches  of  Ludwig  and  his  pupils 
were  formerly  believed  to  prove  that  the  lymph  is  derived  directly  from  the 
plasma  of  the  blood  mainly  by  filtration  through  the  capillary  walls.  Emphasis 
was  laid  on  the  undoubted  fact  that  the  blood  within  the  capillaries  is  under 
a  pressure  higher  than  that  prevailing  in  the  tissues  outside,  and  it  was  Hip- 
posed  that  this  excess  of  pressure  is  sufficient  to  squeeze  the  plasma  of  the 
blood  through  the  very  thin  capillary  walls.  Various  conditions  that  alter 
the  pressure  of  the  blood  were  shown  to  influence  the  amount  of  lymph 
formed  in  accordance  with  the  demands  of  a  theory  of  filtration.  More- 
over, the  composition  of  lymph  as  usually  given  seems  to  support  such  :i 
theory,  inasmuch  as  the  inorganic  salts  contained  in  it  are  in  the  same  concen- 
tration, approximately,  as  in  blood-plasma,  while  the  proteids  are  in  less  con- 
centration, following  the  well-known  law  that  in  the  filtration  of  colloids 
throueh  animal  membranes  the  filtrate  is  more  dilute  than  the  original  solution. 


72  AX   AMERICAN    TEXT-BOOK    OE  PHYSIOLOGY. 

This  simple  and  apparently  satisfactory  theory  has  been  subjected  to  critical 
examination  within  recent  years,  and  it  has  been  shown  that  filtration  alone 
does  not  suffice  to  explain  the  composition  of  the  lymph  under  all  circum- 
stances. At  present  two  divergent  views  are  held  upon  the  subject.  Accord- 
ing to  some  physiologists,  all  the  facts  known  with  regard  to  the  composition 
of  lymph  may  be  satisfactorily  explained  if  we  suppose  that  this  liquid  is 
formed  from  blood-plasma  by  the  combined  action  of  the  physical  processes 
of  filtration,  diffusion,  and  osmosis.  According  to  others,  it  is  believed  that,  in 
addition  to  filtration  and  diffusion,  it  is  necessary  to  assume  an  active  secretory 
process  on  the  part  of  the  endothelial  cells  composing  the  capillary  walls.  A 
discussion  upon  these  points  is  in  progress  in  current  physiological  literature, 
and  it  is  impossible  to  foresee  definitely  what  the  outcome  will  be,  since  a  final 
conclusion  can  be  reached  only  by  repeated  experimental  investigations.  The 
actual  condition  of  our  knowledge  of  the  subject  can  be  presented  most  easily 
by  briefly  stating  some  of  the  objections  that  have  been  raised  by  Heiden- 
hain1  to  a  pure  filtration-and-diffusion  theory,  and  indicating  how  these  objec- 
tions have  been  met. 

1.  Heidenhain  shows  by  simple  calculations  that  an  impossible  formation 
of  lymph  would  be  required,  upon  the  filtration  theory,  to  supply  the  chemical 
oeeds  of  the  organs  in  various  organic  and  inorganic  constituents.  Thus, 
to  take  an  illustration  that  has  been  much  discussed,  one  kilogram  of  cows' 
milk  contains  1.7  grams  CaO,  and  the  entire  milk  of  twenty-four  hours  would 
contain  in  round  numbers  42.5  grams  CaO.  Since  the  lymph  contains  nor- 
mally about  0.18  parts  of  CaO  per  thousand,  it  would  require  236  liters  of 
lymph  per  day  to  supply  the  necessary  CaO  to  the  mammary  glands.  Heiden- 
hain himself  suggests  that  the  difficulty  in  this  case  may  be  met  by  assuming 
active  diffusion  processes  in  connection  with  filtration.  If,  for  instance,  in  the 
case  cited,  we  suppose  that  the  CaO  of  the  lymph  is  quickly  combined  by  the 
tissues  of  the  mammary  gland,  then  the  tension  of  calcium  salts  in  the  lymph 
will  be  kept  at  zero,  and  an  active  diffusion  of  calcium  into  the  lymph  will  occur 
so  long  as  the  gland  is  secreting.  In  other  words,  the  gland  will  receive  its 
calcium  by  much  the  same  process  as  it  receives  its  oxygen,  and  will  get  its 
daily  supply  from  a  comparatively  small  bulk  of  lymph.  Strictly  speaking, 
therefore,  the  difficulty  we  are  dealing  with  here  shows  only  the  insufficiency 
of  a  pure  filtration  theory.  It  seems  possible  that  filtration  and  diffusion 
together  would  suffice  to  supply  the  organs,  so  far  at  least  as  the  diffusible 
substances  are  concerned. 

2.  Heidenhain  found  that  occlusion  of  the  inferior  vena  cava  causes  not 
only  an  increase  in  the  How  of  lymph — as  might  be  expected,  on  the  filtration 
theory,  from  the  consequent  rise  of  pressure  in  the  capillary  regions — but  also 
an  increased  concentration  in  the  percentage  of  proteid  in  the  lymph.  This 
latter  fact  has  been  satisfactorily  explained  by  the  experiments  of  Starling.2 
According  to  this  observer,  the  lymph  formed  in  the  liver  is  normally  more 

1  Archie  fur  die  gesammte  Physioloffie,  1891,  Bd.  xlix.  S.  209. 
'Journal  of  Physiology,  1894,  vol.  xvi.  p.  234. 


L  YMPII.  73 

concentrated  than  that  of  the  rest  of  the  body.  The  occlusion  of  the  vena 
cava  causes  a  marked  rise  in  the  capillary  pressure  in  the  liver,  and  most  of 
the  increased  lymph-flow  under  these  circumstances  comes  from  the  liver, 
hence  the  greater  concentration.  The  results  of  this  experiment,  therefore,  do 
not  antagonize  the  filtration-and-diff'usion  theory. 

3.  Heidenhein  discovered  that  extracts  of  various  substances  which  he 
designated  as  "  lymphagogues  of  the  first  class"  cause  a  marked  increase  in  the 
flow  of  lymph  from  the  thoracic  duct,  the  lymph  being  more  concentrated  than 
normal,  and  the  increased  flow  continuing  for  a  long  period.  Nevertheless, 
these  substances  cause  little,  if  any,  increase  in  general  arterial  pressure ;  in 
fact,  if  injected  in  sufficient  quantity  they  produce  usually,  a  fall  of  arterial 
pressure.  The  substances  belonging  to  this  class  comprise  such  things  as  pep- 
tone, egg-albumin,  extracts  of  liver  and  intestine,  and  especially  extracts  of  the 
muscles  of  crabs,  crayfish,  mussels,  and  leeches.  Heidenhain  supposed  that 
these  extracts  contain  an  organic  substance  which  acts  as  a  specific  stimulus  to 
the  endothelial  cells  of  the  capillaries  and  increases  their  secretory  action.  The 
results  of  the  action  of  these  substances  has  been  differently  explained  by  those 
who  are  unwilling  to  believe  in  the  secretion  theory.  Starling1  finds  experi- 
mentally that  the  increased  flow  of  lymph  in  this  case,  as  after  obstruction  of 
the  vena  cava,  comes  mainly  from  the  liver.  There  is  at  the  same  time  in  the 
portal  area  an  increased  pressure  that  may  account  in  part  for  the  greater  flow 
of  lymph ;  but,  since  this  effect  upon  the  portal  pressure  lasts  but  a  short  time, 
while  the  greater  flow  of  lymph  may  continue  for  one  or  two  hours,  it  is 
obvious  that  this  factor  alone  does  not  suffice  to  explain  the  result  of  the  injec- 
tions. Starling  suggests,  therefore,  that  these  extracts  act  pathologically 
upon  the  blood-capillaries,  particularly  those  of  the  liver,  and  render  them 
more  permeable,  so  that  a  greater  quantity  of  concentrated  lymph  filters 
through  them.  Starling's  explanation  is  supported  by  the  experiments  of 
Popotf.2  According  to  this  observer,  if  the  lymph  is  collected  simulta- 
neously from  the  lower  portion  of  the  thoracic  duct,  which  conveys  the  lymph 
from  the  abdominal  organs,  and  from  the  upper  part,  which  contains  the 
lymph  from  the  head,  neck,  etc.,  it  will  be  found  that  injection  of  peptone 
increases  the  flow  from  only  the  abdominal  organs.  Popoff  finds  also  that 
the  peptone  causes  a  dilatation  in  the  intestinal  circulation  and  a  marked  rise 
in  the  portal  pressure.  At  the  same  time  there  is  some  evidence  of  injury  to 
the  walls  of  the  blood-vessels  from  the  occurrence  of  extravasations  in  the 
intestine.  As  far,  therefore,  as  the  action  of  the  lymphagogues  of  the  first 
class  is  concerned,  it  maybe  said  that  the  advocates  of  the  filtration-and-diffu- 
sion theory  have  suggested  a  plausible  explanation  in  accord  with  their  theory. 
The  facts  emphasized  by  Heidenhain  with  regard  to  this  class  of  substances  do 
not  compel  us  to  assume  a  secretory  function  for  the  endothelial  cells. 

4.  Injection  of  certain  crystalline  substances,  such  as  sugar,  Xa('l,and 
other  neutral  salts,  causes  a  marked  increase  in  the  (low  of  lymph  from  the 
thoracic  duct.      The  lymph  in  these  cases  is  more  dilute  than  normal,  and  the 

1  Journal  of  Physiology,  L89  I.  vol.  xvii.  p.  30.     '  t  vrdralblatt fur  Physiologic,  L895,  Bd.  Lx.  No.  2. 


74  AN  AMERICAN    TEXT-BOOK    OE  PHYSIOLOGY. 

blood-plasma  also  becomes  more  watery,  thus  indicating  that  the  increase  in 
water  comes  from  the  tissues  themselves.  Heidenhain  designated  these  bodies 
as  "  Ivmphagogues  of  the  second  class."  His  explanation  of  their  action  is 
that  the  crystalloid  materials  introduced  into  the  blood  are  eliminated  by  the 
secretory  activity  of  the  endothelial  cells,  and  that  they  then  attract  water 
from  the  tissue-elements,  thus  augmenting  the  flow  of  lymph.  These  sub- 
stances cause  but  little  change  in  arterial  blood-pressure,  hence  Heidenhain 
thought  that  the  greater  flow  of  lymph  could  not  be  explained  by  an  increased 
filtration.  Starling1  has  shown,  however,  that,  although  these  bodies  may  not 
seriously  alter  general  arterial  pressure,  they  may  greatly  augment  intracapil- 
lary  pressure,  particularly  in  the  abdominal  organs.  His  explanation  of  the 
greater  flow  of  lymph  in  these  cases  is  as  follows  :  "  On  their  injection  into 
the  blood  the  osmotic  pressure  of  the  circulating  fluid  is  largely  increased.  In 
consequence  of  this  increase  water  is  attracted  from  lymph  and  tissues  into  the 
blood  by  a  process  of  osmosis,  until  the  osmotic  pressure  of  the  circulating 
fluid  is  restored  to  normal.  A  condition  of  hydremic  plethora  is  thereby  pro- 
duced, attended  with  a  rise  of  pressure  in  the  capillaries  generally,  especially 
in  those  of  the  abdominal  viscera.  This  rise  of  pressure  will  be  proportional 
to  the  increase  in  the  volume  of  the  blood,  and  therefore  to  the  osmotic  pres- 
sure of  the  solutions  injected.  The  rise  of  capillary  pressure  causes  great 
increase  in  the  transudation  of  fluid  from  the  capillaries,  and  therefore  in  the 
lymph-flow  from  the  thoracic  duct."  This  explanation  is  well  supported  by 
experiments,  and  seems  to  obviate  the  necessity  of  assuming  a  secretory  action 
on  the  part  of  the  capillary  walls. 

5.  One  of  the  most  interesting  facts  developed  by  the  experiments  of  Hei- 
denhain and  his  pupils  is  that  after  the  injection  of  sugar  or  neutral  salts  in 
the  blood  the  percentage  of  these  substances  in  the  lymph  of  the  thoracic  duct 
may  be  greater  than  in  the  blood  itself.  It  is  obviously  difficult  to  explain 
how  this  can  occur  by  filtration  or  diffusion,  since  it  seems  to  involve  the  pas- 
sage of  crystalloid  bodies  from  a  less  concentrated  to  a  more  concentrated  solu- 
tion. Cohnstein  2  has  endeavored  to  show  a  fallacy  in  these  results.  He  con- 
tends that  since  it  requires  some  time  (several  minutes)  for  the  lymph  to  form 
and  pass  into  the  thoracic  duct,  it  is  not  justifiable  to  compare  the  quantitative 
composition  of  specimens  of  blood  and  lymph  taken  at  the  same  time.  If  one 
compares,  in  any  given  experiment,  the  maximal  percentage  in  the  blood  of 
the  substance  injected  with  its  maximal  percentage  in  the  lymph,  the  latter 
will  be  found  to  be  lower.  This,  however,  does  not  seem  to  be  the  case  in  all 
the  experiments  reported.  The  work  of  Mendel s  with  sodium  iodide  seems  to 
establish  the  fact  that  when  this  salt  is  injected  slowly  its  maximal  percentage 
in  the  lymph  may  exceed  that  in  the  blood;  and  in  the  experiments  made  by 
Cohnstein,  as  well  as  those  by  Mendel,  it  is  shown  that  the  percentage  of  the 
substance  in  the  lymph  remains  above  that  in  the  blood  throughout  most  of 
the  experiment.      In  this  point,  therefore,  there  seems  to  be  a  real  difficulty  in 

1  Op.  fit.  2Archiv  fur  die  cjemmmtc  Physiologie,  1894-95,  Bole,  lix.,  lx.  and  lxii. 

s  Journal  nf  Phi/xiology,  1896,  vol.  xix.  p.  227. 


L  YMPH.  75 

the  direct  application  of  the  laws  of  filtration  and  diffusion  to  the  explanation 
of  the  composition  of  lymph,  but  it  is  a  point  upon  which  more  information 
is  necessary  before  it  alone  can  be  accepted  as  a  basis  for  a  secretion  theory. 
Meanwhile  it  seems  evident  that  in  spite  < » t*  the  very  valuable  work  of 
Heidenhain,  which  has  added  so  much  to  our  knowledge  of  the  conditions 
influencing;  the  formation  of  lymph,  the  existence  of  a  definite  secretory 
activity  of  the  endothelial  cells  of  the  capillaries  has  not   been   proved. 

Summary  of  the  Factors  Controlling-  the  Flow  of  Lymph. — We  may, 
therefore,  adopt,  provisionally  at  least,  the  so-called  mechanical  theory  of  the 
origin  of  lymph.  Upon  this  theory  the  forces  in  activity  are,  first,  the  intra- 
capillary  pressure  tending  to  filter  the  plasma  through  the  endothelial  cells 
composing  the  walls  of  the  capillaries;  second,  the  force  of  diffusion  depend- 
ing upon  the  inequality  in  chemical  composition  of  the  blood-plasma  and  the 
liquid  outside  the  capillaries,  or,  on  the  other  side,  between  this  liquid  ami 
the  contents  of  the  tissue-elements;  third,  the  force  of  osmotic  pressure. 
These  three  forces  acting  everywhere  control  primarily  the  amount  and  com- 
position of  the  lymph,  but  still  another  factor  must  be  considered.  For  when 
we  come  to  examine  the  flow  of  lymph  in  different  parts  of  the  body  striking 
differences  are  found.  It  has  been  shown,  for  instance,  that  in  the  limbs, 
under  normal  conditions,  the  flow  is  extremely  scanty,  while  from  the  liver 
and  the  intestinal  area  it  is  relatively  abundant.  In  fact,  the  lymph  of  the 
thoracic  duct  may  be  considered  as  being  derived  almost  entirely  from  the 
latter  two  regions.  Moreover,  the  lymph  from  the  liver  is  characterized  by 
a  greater  percentage  of  proteids.  To  account  for  these  differences  Starling 
suggests  the  plausible  explanation  of  a  variation  in  permeability  in  the  capil- 
lary walls.  The  capillaries  seem  to  have  a  similar  structure  all  over  the 
body  so  far  as  this  is  revealed  to  us  by  the  microscope,  but  the  fact  that  the 
lymph-flow  varies  so  much  in  quantity  and  composition  indicates  that  the 
similarity  is  only  superficial,  and  that  in  different  organs  the  capillary  walls 
may  have  different  internal  structures,  and  therefore  different  permeabilities. 
This  factor  is  evidently  one  of  great  importance.  From  the  foregoing  con- 
siderations it  is  evident  that  changes  in  capillary  pressure,  however  produced, 
may  alter  the  flow  of  lymph  from  the  blood-vessels  to  the  tissues, by  increas- 
ing or  decreasing,  as  the  case  may  be,  the  amount  of  filtration  :  changes  in 
the  composition  of  the  blood,  such  as  follow  periods  of'  digestion,  will  cause 
diffusion  and  osmotic  streams  tending  to  equalize  the  composition  of  blood 
and  lymph;  and  changes  in  the  tissues  themselves  following  upon  physio- 
logical or  pathological  activity  will  also  disturb  the  equilibrium  of  composi- 
tion, and,  therefore,  set  up  diffusion  and  osmotic  currents.  In  this  way  a 
continual  interchange  is  taking  place  by  means  of  which  the  nutrition  of  the 
tissues  is  effected,  each  according  to  its  needs.  The  details  of  this  interchange 
must  of  necessity  be  very  complex  when  we  consider  the  possibilities  of  local 
effects  in  different  parts  of  the  body.  The  total  effects  of  general  changes, 
such  as  may  be  produced  experimentally,  are  simpler,  and,  as  we  have  Been, 
are  explained  satisfactorily  by  the  physical  and  chemical  factors  enumerated. 


III.  CIRCULATION. 


PA  IiT  I.— THE  MECHANICS  OF  THE  CIRCULATION  OF  THE 
BLOOD  AND  OF  THE  MOVEMENT  OF  THE  LYMPH. 

A.  General  Considerations. 

The  metaphorical  phrase  "  circulation  of  the  blood"  means  that  every  par- 
ticle of  blood,  so  long  as  it  remains  within  the  vessels,  moves  along  a  path 
which,  no  matter  how  tortuous,  finally  returns  into  itself ;  that,  therefore,  the 
particles  which  pass  a  given  poiut  of  that  path  may  be  the  same  which  have 
passed  it  many  times  already ;  and  that  the  blood  moves  in  its  path  always  in 
a  definite  direction,  and  never  in  the  reverse. 

The  discoverer  of  these  weighty  facts  was  "  William  Harvey,  physician, 
of  London,"  as  he  styled  himself.  In  the  lecture  notes  of  the  year  1616, 
mostly  in  Latin,  which  contain  the  earliest  record  of  his  discovery,  he  declares 
that  a  "  perpetual  movement  of  the  blood  in  a  circle  is  caused  by  the  beat  of 
the  heart"  ("perpetuum  sanguinis  motum  in  circ'ulo  fieri  pulsu  cordis").1 
For  a  long  time  afterward  the  name  of  the  discoverer  was  coupled  with  the 
expression  which  he  himself  had  introduced,  and  the  true  movement  of  the 
blood  was  known  as  the  "Harveian  circulation."2 

Course  of  the  Blood. — The  metaphorical  circle  of  the  blood-path  may 
be  shown  by  such  a  diagram  as  Figure  8. 

If,  in  the  body  of  a  warm-blooded  animal,  we  trace  the  course  of  a  given 
particle,  beginning  at  the  point  where  it  leaves  the  right  ventricle  of  the  heart, 
we  find  that  course  to  be  as  follows  :  From  the  trunk  of  the  pulmonary  artery 
(PA)  through  a  succession  of  arterial  branches  derived  therefrom  into  a  capil- 
lary of  the  lungs  (PC) ;  out  of  that,  through  a  succession  of  pulmonary  veins,  to 
one  of  the  main  pulmonary  veins  (PF)  and  the  left  auricle  of  the  heart  (L A) ; 
thence  to  the  left  ventricle  (LV);  to  the  truuk  of  the  aorta  (A);  through  a 
succession  of  arterial  branches  derived  therefrom  into  any  capillary  (C)  not 
supplied  by  the  pulmonary  artery;  out  of  that,  through  a  succession  of  veins 
(F)  to  one  of  the  vena?  cava?  or  to  a  vein  of  the  heart  itself;  thence  to  the 
right  auricle  (RA),  to  the  right  ventricle  (RV),  and  to  the  trunk  of  the  pul- 
monary  artery,  where  the  tracing  of  the  circuit  began. 

1  William  Harvey:  Prelectione.s  Anatomies,  Universal!*,  edited,  with  an  autotype  reproduction 
of  the  original,  by  a  committee  of  the  Royal  College  of  Physicians  "f  London,  1886,  p.  80. 

J  Harvey's  discovery  of  the  circulation  was  first  published  in  the  modern  sense  in  his  work 
Exercitalio  amaiomica  de  motu  cordis  ei  sanguinis  in  animalibus,  Francofurti,  1628.    This  great 
classic  <:ui  he  read  in  English  in  the  following  :  On  the  Motion  of  the  Heart  and  Blood  in  Animals. 
By  William  Harvey,  M.  D. ;  Willis's  translation,  revised  and  edited  by  Alex.  Bowie,  1889. 
76 


CIRCULATION. 


77 


It  must  be  noted  here  that  a  particle  of  blood  which  traverses  a  capillary 
of  the  spleen,  of  the  pancreas,  of  the  stomach,  or  of  the  intestines,  and  enters 
the  portal  vein,  must  next  traverse  a  series  of  venous  branches  of  diminishing 
size,  and  a  capillary  of  the  liver,  before  entering  the  succession  of  veins  which 
will  conduct  the  particle  to  the  ascending  vena  cava  (compare  Figs.  8  and  9). 

Most  of  the  blood,  therefore,  which 
leaves  the  liver  has  traversed  two  sets 
of  capillaries,  connected  with  one 
another  by  the  portal  vein,  since  quit- 
ting  the  arterial    system.      This   ar- 


Fig.  8. — General  diagram  of  the  circulation : 
the  arrows  indicate  the  course  of  the  blood:  PA, 
pulmonary  artery ;  P  C,  pulmonary  capillaries  ; 
P  V,  pulmonary  veins ;  L  A,  left  auricle  ;  L  V,  left 
ventricle  ;  A,  systemic  arteries ;  C,  systemic  capil- 
laries ;  V,  systemic  veins  ;  R  A,  right  auricle  ;  R  V, 
right  ventricle. 


Fig.  9. — Diagram  of  the  portal  system :  the  ar- 
rows indicate  the  course  of  the  blood:  A,  arterial 
system ;  V,  venous  system :  C,  capillaries  of  the 
spleen,  pancreas,  and  alimentary  canal;  P  V,  portal 
vein;  C",  capillaries  of  the  liver  ;  C,  the  rest  of  the 
systemic  capillaries.  The  hepatic  artery  is  not 
represented. 


rangement  is  of  extreme  importance  for  the  physiology  of  nutrition.  An 
arrangement  of  the  same  order,  though  less  conspicuous,  exists  in  the 
kidney. 

Causes  of  the  Blood-flow. — The  force  by  which  the  blood  is  driven  from 
the  right  to  the  left  side  of  the  heart  through  the  capillaries  which  are  related 
to  the  respiratory  surface  of  the  lungs,  is  nearly  all  derived  from  the  contrac- 
tion of  the  muscular  wall  of  the  right  ventricle,  which  narrows  the  cavity 
thereof  and  ejects  the  blood  contained  in  it;  the  force  by  which  the  blood  is 
driven  from  the  left  to  the  right  side  of  the  heart  through  all  the  other  capil- 
laries of  the  body,  often  called  the  "systemic"  capillaries,  is  derived  nearly 
all  from  the  contraction  of  the  muscular  wall  of  the  left  ventricle,  which  nar- 
rows its  cavity  and  ejects  its  contents.  The  contractions  of  the  two  ventricles 
are  simultaneous.  The  force  derived  from  each  contraction  is  generated  by 
the  conversion  of  potential  energy,  present  in  the  chemical  constituents  of  the 
muscular  tissue,  into  energy  of  visible  motion;  a  part  also  of  the . potential 
energy  at  the  same  time  becoming  manifest  as  heat.  In  the  maintenance  of 
the  circulation  the  force  generated  by  the  heart  is  to  a  very  subordinate  degree 
supplemented  by  the  forces  which  produce  the  aspiration  of  the  chest  and  by 


78  AJV    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

the  force  generated  by  the  contractions  of  the  skeletal  muscles  throughout  the 
body  (sec  p.  95). 

Mode  of  Working-  of  the  Pumping-  Mechanism. — During  each  contrac- 
tion or  "systole"  of  the  ventricles  the  blood  is  ejected  into  the  arteries  only, 
because  at  that  time  the  auriculo-ventricular  openings  are  each  closed  by  a  valve. 
During  the  immediately  succeeding  "diastole"  of  the  ventricles,  which  con- 
sists in  the  relaxation  of  their  muscular  walls  and  the  dilatation  of  their 
cavities,  blood  enters  the  ventricles  by  way  of  the  auricles  only,  because  at  that 
time  the  arterial  openings  are  closed  each  by  a  valve  which  was  open  duriug 
the  ventricular  systole  ;  and  because  the  auriculo-ventricular  valves  which 
were  closed  during  the  systole  of  the  ventricles  are  open  during  their  diastole. 
During  the  first  and  longer  part  of  the  diastole  of  the  ventricles  the  auricles, 
too,  are  in  diastole  ;  the  whole  heart  is  in  repose;  and  blood  is  not  only  enter- 
ing the  auricles,  but  passing  directly  through  them  into  the  ventricles. 
Near  the  end  of  the  ventricular  diastole  a  brief  simultaneous  systole  of  both 
auricles  takes  place,  during  which  they,  too,  narrow  their  cavities  by  the 
muscular  contraction  of  their  walls,  and  eject  into  the  ventricles  blood  which 
had  entered  the  auricles  from  the  "  systemic "  and  pulmonary  veins  respec- 
tively. The  systole  of  the  auricles  ends  immediately  before  that  of  the  ventri- 
cles begins.  The  brief  systole  of  the  auricles  is  succeeded  by  their  long  dias- 
tole, which  corresponds  in  time  with  the  whole  of  the  ventricular  systole  aud 
with  the  greater  part  of  the  succeeding  ventricular  diastole.  During  the  dias- 
tole of  the  auricles  blood  is  entering  them  out  of  the  veins.  Thus  it  is  seen 
that  the  direction  in  which  the  blood  is  forced  is  essentially  determined  by  the 
mechanism  of  the  valves  at  the  apertures  of  the  ventricles;  and  that  it  is  due 
to  these  valves  that  the  blood  moves  only  in  the  definite  direction  before 
alluded  to.  In  the  words,  again,  of  Harvey's  note-book,  at  this  point  written 
in  English,  the  blood  is  perpetually  transferred  through  the  lungs  into  the 
aorta  "  as  by  two  clacks  of  a  water  bellows  to  rayse  water."1 

Pulmonary  Blood-path. — In  the  birds  and  mammals  the  entire  breadth  of 
the  blood-path,  at  one  part  of  the  physiological  circle,  consists  in  the  capillaries 
spread  out  beneath  the  respiratory  surface  of  the  lungs.  The  right  side  of  the 
heart  exists  only  to  force  the  blood  into  aud  past  this  portion  of  its  circuit, 
where,  as  in  the  systemic  capillaries,  the  friction  due  to  the  fineness  of  the  tubes 
causes  much  resistance  to  the  flow.  This  great  comparative  development  of  the 
pulmonary  portion  of  the  blood-path  in  the  warm-blooded  vertebrates  is  related 
to  the  activity,  in  them,  of  the  respiration  of  the  tissues,  which  calls  for  a  cor- 
responding activity  of  function  at  the  respiratory  surface  of  the  lungs,  and  fora 
rapid  renewal  in  every  systemic  capillary  of  the  internal  respiratory  medium,  the 
blood.  This  rapid  renewal  implies  a  rapid  circulation;  and  that  the  speed  is 
great  with  which  the  circuit  of  the  heart  and  vessels  is  completed  has  been 
proven  by  experiment,  the  method  being  too  complicated  for  description  here.2 

1  /'  etc.,  p.  80. 

2  K:irl  Vierordt:  Die  Erscheinungen  und  Gesetze  der  Stromgeschwindujkeiten  des  Blules.  2te 
Ausgabe,  1882. 


CIRCULATION.  79 

Rapidity  of  the  Circulation. — By  experiment  the  shortest  time  has  been 
measured  which  is  taken  by  a  particle  of  blood  in  passing  from  a  point  in  the 
external  jugular  vein  of  a  dog  to  and  through  the  right  cavities  of  the  heart, 
the  pulmonary  vessels,  the  left  cavities  of  the  heart,  the  commencement  of 
the  aorta,  and  the  arteries,  capillaries,  and  veins  of  the  head,  to  the  starting- 
point,  or  to  the  same  point  of  the  vein  of  the  other  side.  This  time  has 
been  found  to  be  from  fifteen  to  eighteen  seconds.  Naturally,  the  time  would 
be  different  in  different  kinds  of  animals  and  in  the  different  circuits  in  the 
same  individual. 

Order  of  Study  of  the  Mechanics  of  the  Circulation. — The  significance 
and  the  fundamental  facts  of  the  circulation  have  now  been  indicated.  Its 
phenomena  must  next  be  studied  in  detail.1  .  As  the  blood  moves  in  a  circle, 
we  may,  in  order  to  study  the  movement,  strike  into  the  circle  at  any  point. 
It  will,  however  be  found  both  logical  and  instructive  to  study  first  the  move- 
ment of  the  blood  in  the  capillaries,  whether  systemic  or  pulmonary.  It  is 
only  in  passing  through  these  and  the  minute  arteries  and  veins  adjoining  that 
the  blood  fulfils  its  essential  functions;  elsewhere  it  is  in  transit  merely. 
Moreover,  it  is  only  in  the  minute  vessels  that  the  blood  and  the  nature  of 
its  movement  are  actually  visible. 

After  the  capillary  flow  shall  have  become  familiar,  it  will  be  found  that 
the  other  phenomena  of  the  circulation  will  fall  naturally  into  place  as  indi- 
cating how  that  flow  is  caused,  is  varied,  and  is  regulated. 

B.  The  Movement  of  the  Blood  in  the  Capillaries  and  in  the 
Minute  Arteries  and  Veins. 

Characters  of  the  Capillaries. — Each  of  the  vessels  which  compose  the 
immensely  multiplied  capillary  network  of  the  body  is  a  tube,  commonly  of 
less  than  one  millimeter  in  length,  and  of  a  few  one-thousandths  only  of  a 
millimeter  in  calibre,  the  wall  of  which  is  so  thin  as  to  elude  accurate  measure- 


Fig.  10.— A  capillary  from  the  mesentery  of  the  frog  (Ranvier). 

ment.  The  calibre  of  each  capillary  may  vary  from  time  to  time.  These 
facts  indicate  the  minute  subdivision  of  the  blood-stream  in  the  lungs,  and 
among  the  tissues — that  is,  at  the  two  points  of  its  course  where  the  essential 
functions  of  the  blood  are  fulfilled.     These  facts  also  show  the  shortness  of 

1  The   following  is   a  very  valuable   book  of  reference:   Kobert  Tigerstedt:  Lehrbuch  der 
Physiologie  des  Kreislaufes,  1893. 


80  AN  AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

the  distance  to  be  traversed  by  the  blood  while  fulfilling  these  functions; 
and  explain  the  importance  of  the  comparatively  slow  rate  at  which  it  will  be 
found  to  move  through  that  short  distance.  The  histological  study  of  a  typ- 
ical capillary  (see  Fig.  10)  shows  that  its  thin  wall  is  composed  of  a  single 
layer  only  of  living  flat  endothelial  cells  set  edge  to  edge  in  close  contact;  and 
that  the  edges  of  the  cells  are  united  by  a  small  quantity  of  the  so-called 
cement-substance.  If  the  capillary  be  traced  in  either  anatomical  direction, 
the  wall  of  the  vessel  is  seen  to  become  less  thin  and  more  complex,  till  it 
merges  into  that  of  a  typical  arteriole  or  venule,  the  walls  of  which  are  still 
delicate,  though  less  so  than  that  of  a  capillary.  That  the  capillary  walls  are 
so  thin  and  soft,  and  are  made  of  living  cells,  are  very  important  facts  as 
regards  the  relations  between  blood  and  tissue.  It  is  of  great  importance 
for  the  variation  of  the  blood-supply  to  a  part  that  they  are  also  distensible, 
elastic,  and  possibly  contractile. 

Direct  Observation  of  the  Flow  in  the  Small  Vessels. — The  capillary 
flow  is  visible  under  the  compound  microscope,  best  by  transmitted  light,  in 
the  transparent  parts  of  both  warm-blooded  and  cold-blooded  animals.  It  is 
important  that  the  phenomena  observed  in  the  latter  should  be  compared  with 
observations  upon  the  higher  animals  ;  but  the  fundamental  facts  can  be  most 
fruitfully  studied  in  the  frog,  tadpole,  or  fish,  inasmuch  as  no  special  arrange- 
ments are  needed  to  maintain  the  temperature  of  the  exposed  parts  of  these 
animals.  Moreover,  their  large  oval  and  nucleated  red  blood-corpuscles  are 
well  fitted  to  indicate  the  forces  to  which  they  are  subjected.  The  capillary 
movement,  therefore,  will  be  described  as  seen  in  the  frog;  it  being  under- 
stood that  the  phenomena  are  similar  in  the  other  vertebrates.  In  the 
frog  the  movement  may  be  studied  in  the  lung,  the  mesentery,  the  urinary 
bladder,  the  tongue,  or  the  web  between  the  toes.  During  such  study  the 
proper  wall  of  the  living  capillary  is  hardly  to  be  seen,  but  only  the  line  on 
each  side  which  marks  the  profile  of  its  cavity.  Even  the  proper  walls  of 
the  transparent  arterioles  and  venules  arc  but  vaguely  indicated.  The  plasma 
of  the  blood,  too,  has  so  nearly  the  same  index  of  refraction  as  the  tissues, 
that  it  remains  invisible.  It  is  only  the  red  corpuscles  and  leucocytes  that 
are  conspicuous;  and  when  one  speaks  of  seeing  the  blood  in  motion,  he  means, 
strictly  speaking,  that  he  sees  the  moving  corpuscles,  and  can  make  out  the 
calibre  of  the  vessels  in  which  they  move.  The  observer  uses  as  low  a  power 
of  the  microscope  as  will  suffice,  and  takes  first  a  general  survey  of  the  minute 
arteries,  veins,  and  capillaries  of  the  part  he  is  studying,  noting  their  form, 
size,  and  connections.  In  the  arteries  and  veins  he  sees  that  the  size  of  the 
vessels  is  ample  in  comparison  with  that  of  the  corpuscles  ;  that,  in  the  veins, 
the  movement  of  the  blood  is  steady,  but  in  the  arteries  accelerated  and 
retarded,  with  a  rhythm  corresponding  to  that  of  the  heart's  beat.  In  some 
part-,  if  the  circumstances  of  the  observation  have  somewhat  retarded  the 
circulation,  the  individual  red  corpuscles  can  be  distinguished  in  the  veins, 
while  in  the  arteries  they  cannot,  as  at  all  times  they  shoot  past  the  eye  too 
swiftly.  The  fundamental  observation  now  is  verified  that  the  blood  is 
incessantly  moving  out  of  the  arteries,  through  the  capillaries,  into  the  veins. 


CIRCULA  TION. 


81 


Behavior  of  the  Red  Corpuscles. — Capillaries  will  readily  he  found  in 
which  the  red  corpuscles  move  two  or  three  abreast,  or  only  in  single  file. 
They  generally  go  with  their  long  diameters  parallel  to,  or  moderately  oblique 
to,  the  current.  In  no  case  will  any  blockade  of  corpuscles  occur,  so  long  as 
the  parts  are  normal.  The  numerous  red  corpuscles  are  seen  to  be  well  fitted 
by  their  softness  and  elasticity,  as  well  as  by  their  form  and  size,  for  moving 
through  the  narrow  channels.  They  bend  easily  upon  themselves  as  they 
turn  sharp  corners,  but  instantly  regain  their  form  when  free  to  do  so  (see 
Fig.  11).  A  very  common  occurrence  is  for  a  corpuscle  to  catch  upon  the 
edge  which  parts  two  capillaries  at  a  bifurcation  of  the  network.  For  some 
time  the  corpuscle  may  remain  doubled  over  the  projection  like  a  sack  thrown 
across  a  horse's  back  ;  but,  after  oscillating  for  a  while,  it  will  be  disengaged, 
at  once  return  to  its  own  shape,  and  disappear  in  one  of  the  two  branches 


Fig.  II.— To  illustrate  the  behavior  of  red  cor- 
puscles in  the  capillaries :  the  arrows  mark  the 
course  of  the  blood:  a,  a  "saddle-bag';  corpus- 
cle; b,  a  corpuscle  bending  upon  itself  as  it 
enters  a  side  branch. 


Fig.  12— To  illustrate  the  deformity  pro- 
duced in  red  corpuscles  in  passing  through 
a  capillary  of  a  less  diameter  than  them- 
selves. 


(see  Fig.  11).  It  is  instructive  to  watch  red  corpuscles  passing  in  single  file 
through  a  capillary  the  calibre  of  which,  at  the  time,  is  actually  less  than  the 
shorter  diameter  of  the  corpuscles.  Through  such  a  capillary  each  corpuscle 
is  squeezed,  with  lengthening  and  narrowing  of  its  soft  mass,  but  on  emerging 
into  a  larger  vessel  its  elasticity  at  once  corrects  even  this  deformity  ;  it  regains 
its  form,  and  passes  on  (Fig.  12). 

Evidences  of  Friction. — In   the  minute  vessels,  capillary  and  other,  cer- 
tain appearances  should  carefully  be  observed   which  arc  the  direct  ocular 

evidence  of  that  friction  which  we  shall  find  to  be  one  of  the  prime  forces 
concerned  in  the  blood-moveinent,  to  which  it  constitutes  a  strong  resistance. 
If,  in  a  channel  which  admits  three  red  corpuscles  beside  one  another,  three 
be  observed  when  just  abreast,  it  will  be  found  that  very  soon  the  middle  one 
forges  ahead,  indicating  that  the  stream  is  swiftesi  at  its  core.  This  is  because 
the  friction  within  the  vessel  is  least  in  the  middle,  and  progressively  greater 
outward  to  the  wall  (Fig.  13).      in   the  small  veins  the  signs  of  friction   are 

Vol.  I.— 6 


82  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

strikingly  seen,  as  the  outer  layers  among  the  numerous  corpuscles  lag  con- 
spicuously. In  the  arterioles  similar  phenomena  are  seen  if  the  normal  swift- 
ness of  movement  become  sufficiently  retarded  for  the  individual  corpuscles 
to  be  visible. 


Fig.  13.— To  illustrate  the  forging  ahead  of  a  Fig.  14.— The  inert  layer  of  plasma  in  the 

corpuscle  at  the  centre  of  the  blood-stream.  small  vessels. 

The  arrow  marks  the  direction  of  the  blood. 

Aii  appearance  which  also  tells  of  friction  is  that  of  the  so-called  "inert 
layer"  of  plasma.1  In  vessels,  of  whatever  kind,  which  are  wide  enough  for 
several  corpuscles  to  pass  abreast,  it  is  seen  that  all  the  red  corpuscles  are  always 
separated  from  the  profile  of  their  channel  by  a  narrow  clear  and  colorless 
interval — occupied,  of  course,  by  plasma.  This  is  caused  by  the  excess  of  the 
friction  in  the  layers  nearest  to  the  vascular  wall  (see  Fig.  14).  The  friction 
thus  indicated,  other  things  being  equal,  is  less  in  a  dilated  than  in  a  con- 
tracted tube ;  and  less  in  a  sluggish  than  in  a  rapid  stream.  It  probably 
varies  also  with  changes  of  an  unknown  kind  in  the  condition  of  the  cells  of 
the  vascular  wall. 

Behavior  of  the  Leucocytes. — If  the  behavior  of  the  leucocytes  be 
watched,  it  will  be  seen  to  differ  markedly  from  that  of  the  red  corpuscles,  at 
least  when  the  blood-stream  is  somewhat  retarded,  as  it  so  commonly  is  under 
the  microscope.  Whereas  the  friction  within  the  vessels  causes  the  throng  of 
red  corpuscles  to  occupy  the  core  of  the  stream,  the  scantier  leucocytes  may 
move  mainly  in  contact  with  the  wall,  and  thus  be  present  freely  in  the  inert 
layer  of  plasma.  Naturally  their  progression  is  then  much  slower  and  more 
irregular  than  that  of  the  red  disks.  Indeed,  the  leucocytes  often  adhere  to 
the  wall  for  a  while,  in  spite  of  shocks  from  the  red  cells  which  pass  them. 
Moreover,  the  spheroidal  leucocyte  rolls  over  and  over  as  it  moves  along  the 
wall  in  a  way  very  different  from  the  progression  of  the  red  disk,  which  only 
occasionally  may  revolve  about  one  of  its  diameters.  A  leucocyte  entangled 
among  the  red  cells  near  the  middle  of  the  stream  is  seen  generally  not  only 
to  move  onward  but  also  to  move  outward  toward  the  wall,  and,  before  long, 
to  join  the  other  leucocytes  which  are  bathed  by  the  inert  layer  of  plasma. 
h  i-  due  solely  to  tin;  lighter  specific  gravity  of  the  leucocytes  that,  under 
the  forces  at  work  within  the  smaller  vessels,  they  go  to  the  wall,  while  the 
denser  disks  go  to  the  core  of  the  current.  This  has  been  proved  experimen- 
tally by  driving  through  artificial  capillaries  a  fluid  having  in  suspension  par- 
ticles of  two  kind-.     Those  of  the  lighter  kind  go  to  the  wall,  of  the  heavier 

1  Poiseuille:  "Recherches  sur  les  causes  dn  mouvement  du  sang  dans  les  vaisseaux  capil- 
laires,"  Academie  des  Sciences — Savons  etrangers,  1835. 


CIRCULATION.  83 

kind  to  the  core,  even  when  the  nature  and  form  of  the  particles  employed 
are  varied.1 

Emigration  of  Leucocytes. — It  has  been  said  that  a  leucocyte  may  often 
adhere  for  a  time  to  the  wall  of  the  capillary,  or  of  the  arteriole  or  venule, 
in  which  it  is.  Sometimes  the  leucocyte  not  only  adheres  to  the  wall,  but 
passes  through  it  into  the  tissue  without  by  a  process  which  has  received  the 
name  of  "emigration."2  A  minute  projection  from  the  protoplasm  of  the 
leucocyte  is  thrust  iuto  the  wall,  usually  where  this  consists  of  the  sofl  cement- 
substance  between  the  endothelial  cells.  The  delicate  pseudopod  is  seen  pres- 
ently to  have  pierced  the  wall,  to  have  grown  at  the  expense  of  the  main  body 
of  the  cell,  and  to  have  become  knobbed  at  the  free  end  which  i-  in  the  tissue. 
Later,  the  flowing  of  the  protoplasm  will  have  caused  the  leucocyte  to  assume 
something  of  a  dumb-bell  form,  with  one  end  within  the  blood-vessel  and  the 
other  without.  Then,  by  converse  changes,  the  flowing  protoplasm  come-  to 
lie  mainly  within  the  lymph-space,  with  a  small  knob  only  within  the  vessel; 
and,  lastly,  this  knob  too  flows  out;  what  had  been  the  neck  of  the  dumb-bell 
shrinks  and  is  withdrawn  into  the  cell-body,  and  the  leucocyte  now  lies  wholly 
without  the  blood-vessel,  while  the  minute  breach  in  the  soft  wall  has  closed 
behind  the  retiring  pseudopod.  This  phenomenon  has  been  seen  in  capillaries, 
venules,  and  arterioles,  but  mainly  in  the  two  former.  It  seems  to  be  due  to 
the  amoeboid  properties  of  the  leucocytes  as  well  as  to  purely  physical 
causes.  Emigration,  although  it  may  probably  occur  in  normal  vessels,  is 
strikingly  seen  in  inflammation,  in  which  there  seems  to  be  an  increased 
adhesiveness  between  the  vascular  wall  and  the  various  corpuscles  of  the 
blood. 

Speed  of  the  Blood  in  the  Minute  Vessels. — As  a  measure  of  the  speed 
of  the  blood  in  a  vessel,  we  may  fairly  take  the  speed  of  the  red  corpuscles. 
It  must,  however,  be  remembered  that  as  the  friction  increases  toward  the  wall, 
the  speed  of  the  red  corpuscles  is  least  in  the  outer  layers  of  blood,  and  in- 
creases rapidly  toward  the  long  axis  of  the  tube.  At  the  core  of  the  stream  the 
speed  may  be  twice  as  great  as  near  the  wall.  As  we  have  seen,  the  stream  of  red 
corpuscles  in  an  arteriole  is  rapid  and  pulsating.  In  the  corresponding  venule, 
which  is  commonly  a  wider  vessel,  the  stream  is  less  swift,  and  its  pulse  ha-  dis- 
appeared. In  the  capillary  network  between  the  two  vessels  tiie  speed  of  the  red 
corpuscles  is  evidently  slower  than  in  either  arteriole  or  venule  ;  and  here,  as  in 
the  veins,  no  pulse  is  to  be  seen;  the  pulse  comes  to  an  end  with  the  artery 
which  exhibits  it.  In  one  capillary  of  the  network  under  observation  the 
movement  may  be  more  active  than  in  another;  and  even  in  a  given  capillary 
irregular  variations  of  speed  at  different  moments  may  be  observed.  Where 
two  capillaries  in  which  the  pressure  is  nearly  the  same  are  connected  bj  a 
cross-branch,  the    red  corpuscles   in   this  last    may  sometime-  even    be   seen   to 

1  A.  Scliklarewsky -.  "Ueberda-  I'.lut  und  die  Suspensionsfliissigkeiten,"  Pfluger'a  Archivfur 
die gesammte  Physiologie,  1868,  Bd.  i.  8.603. 

'2  For  the  literature  of  emigration  Bee  ri.Tb.oma:  Text-book  of  General  Pathology  and  r<tth><- 
logical  Anatomy,  translated  by  A.  Bruce,  L896,  vol.  i.  \>.  344. 


84  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

oscillate,  conie  to  a  standstill,  and  then  reverse  the  direction  of  their  move- 
ment, and  return  to  the  capillary  whence  they  had  started.  Naturally,  no 
such  reversal  will  ever  be  seen  in  a  capillary  which  springs  directly  from  an 
artery  or  which  directly  joins  a  vein.  It  will  be  remembered,  however,  that 
any  apparent  speed  of  a  corpuscle  is  much  magnified  by  the  microscope,  aud 
thai  therefore  the  variations  referred  to  are  comparatively  unimportant.  We 
may,  in  fact,  without  material  error,  treat  the  speed  of  the  blood  in  the  capil- 
laries which  intervene  between  the  arteries  and  veins  of  a  region  as  approxi- 
mately uniform  for  an  ordinary  period  of  observation,  as  the  minute  varia- 
tions will  tend  to  compensate  for  one  another.  This  speed  is  sluggish,  as 
alreadv  noted.  In  the  capillaries  of  the  web  of  the  frog's  foot  it  has  beeu 
found  to  be  about  0.5  millimeter  per  second.  The  causes  of  this  sluggishness 
will  be  set  forth  later.  That  the  very  short  distance  between  artery  and  vein 
is  traversed  slowly,  deserves  to  be  insisted  on,  as  thus  time  is  afforded  for  the 
uses  of  the  blood  to  be  fulfilled. 

Capillary  Blood-pressure. — The  pressure  of  the  blood  against  the  capil- 
lary wall  is  low,  though  higher  than  that  of  the  lymph  without.  This  pres- 
sure is  subject  to  changes,  and  is  readily  yielded  to  by  the  elastic  and  deli- 
cate wall.  From  these  changes  of  pressure  changes  of  calibre  result.  The 
microscope  tells  us  less  about  the  capillary  blood-pressure  than  about  the  other 
phenomena  of  the  flow;  but  the  microscope  may  sometimes  show  one  striking 
fact.  In  a  capillary  district  under  observation,  a  capillary  not  noted  before 
may  suddenly  start  into  view  as  if  newly  formed  under  the  eye.  This  is 
because  its  calibre  has  been  too  small  for  red  corpuscles  and  leucocytes  to  enter, 
until  some  slight  increase  of  pressure  has  dilated  the  transparent  tube,  hitherto 
filled  with  transparent  plasma  only.  This  dilatation  has  admitted  corpuscles, 
and  has  caused  the  vessel  to  appear. 

That  the  capillary  pressure  is  low  is  shown,  moreover,  by  the  fact  that  when 
one's  linger  is  pricked  or  slightly  cut,  the  blood  simply  drips  away  ;  that  it 
does  not  spring  in  a  jet,  as  when  an  artery  of  any  size  has  been  divided.  That 
the  capillary  pressure  is  low  may  also  be  shown,  and  more  accurately,  by  the 
careful  scientific  application  of  a  familiar  fact:  If  one  press  with  a  blunt 
lead-pencil  upon  the  shin  between  the  base  of  a  finger-nail  and  the  neigh- 
boring joint,  the  ruddy  surface  becomes  pale,  because  the  blood  is  expelled 
from  the  capillaries  and  they  are  flattened.  If  delicate  weights  be  used, 
instead  of  the  pencil,  the  force  can  be  measured  which  just  suffices  to  whiten 
the  surface  somewhat,  that  is,  to  counterbalance  the  pressure  of  the  distend- 
ing blood,  which  pressure  thus  can  be  measured  approximately.  It  has  been 
found  to  be  very  much  lower  than  the  pressure  in  the  large  arteries,  con- 
siderably higher  than  that  in  the  large  veins,  and  thus  intermediate  between 
the  two;  whereas  the  blood-speed  in  the  capillaries  is  less  than  the  speed 
in  either  the  arteries  or  the  veins.  The  pressure  in  the  capillaries,  meas- 
ured by  the  method  just  described,  has  been  found  to  be  equal  to  that 
required  to  sustain  against  gravity  a  column  of  mercury  from  24  to  54  milli- 


CIRCULATION.  85 

meters  high  ;  or,  in  the  parlance  of  the  laboratory,  has  been  found  equal  to 
from  24  to  54  millimeters  of  mercury.1 

Summary  of  the  Capillary  Flow. —  Whether  in  the  Lungs  or  in  the  rest 
of  the  body,  the  general  characters  of  the  capillary  How,  as  learned  from  direct 
inspection  and  from  experiment,  may  be  summed  up  as  follows:  The  blood 
moves  through  the  capillaries  toward  the  veins  with  much  friction,  contin- 
uously, slowly,  without  pulse,  and  under  low  pressure.  To  account  for  these 
facts  is  to  deal  systematically  with  the  mechanics  of  the  circulation  ;  and  to 
that  task  we  must  now  address  ourselves. 

C.  The  Pressure  of  the  Blood  in  the  Arteries,  Capillaries,  and 

Veins. 

Why  does  the  blood  move  continuously  out  of  the  arteries  through  the 
capillaries  into  the  veins?  Because  there  is  continuously  a  high  pressure  of 
blood  in  the  arteries  and  a  low  pressure  in  the  veins,  and  from  the  seat  of  high 
to  that  of  low  pressure  the  blood  must  continuously  flow  through  the  capillaries, 
where  pressure  is  intermediate,  as  already  stated. 

Method  of  Studying-  Arterial  and  Venous  Pressure,  and  General 
Results. — Before  stating  quantitatively  the  differences  of  pressure,  we  must 
see  how  they  are  ascertained  for  the  arteries  and  veins.  The  method  of  obtain- 
ing the  capillary  pressure  has  been  referred  to  already.  If,  in  the  neck  of  a 
mammal,  the  left  common  carotid  artery  be  clamped  in  two  places,  it  can, 
without  loss  of  blood,  be  divided  between  the  clamps,  and  a  long  straight  glass 
tube,  open  at  both  ends,  and  of  small  calibre,  can  be  tied  into  that  stump  of 
the  artery  which  is  still  connected  with  the  aorta,  and  which  is  called  the 
"proximal"  stump.  If  now  the  glass  tube  be  held  upright,  and  the  clamp 
be  taken  off  which  has  hitherto  closed  the  artery  between  the  tube  and  the 
aorta,  the  blood  will  mount  in  the  tube,  which  is  open  at  the  top,  to  a  consid- 
erable height,  and  will  remain  there.  The  external  jugular  vein  of  the  other 
side  should  have  been  treated  in  the  same  way,  but  its  tube  should  have  been 
inserted  into  the  "distal"  stump — that  is,  the  stump  connected  with  the  veins 
of  the  head,  and  not  with  the  subclavian  veins.  If  the  clamp  between  the  tube 
and  the  head  have  been  removed  at  nearly  the  same  time  with  that  upon  the 
artery,  the  blood  may  have  mounted  in  the  upright  venous  tube  also,  but  only 
to  a  small  distance.  To  cite  an  actual  case  in  illustration,  in  a  small  etherized 
dog  the  arterial  blood-column  has  been  seen  to  stand  at  a  height  of  about  loo 
centimeters  above  the  level  of  the  aorta,  the  height  of  the  venous  column 
about  18  centimeters  above  the  same  level.  The  heights  of  the  arterial  and 
venous  columns  of  blood  measure  the  pressures  obtaining  within  the  aorta  and 
the  veins  of  the  head  respectively,  while  at  the  same  time  the  circulation  con- 
tinues to  be  free  through  both  the  aorta  and  the  venous  net  work.  Therefore, 
in  the  dog  above  referred  to,  the  aortic  pressure  was   between   eight   and  nine 

1  N.  v.  Kries :  "Ueberden  Druckinden  Blutcapillaren  der  menschlichen  Haul."  BerichL 
iiber  die  Verhnndlungen  der  k.  sachsischen  Qeselkchaft  der  Wwsenschaften  zu  Leipzig,  math.-physische 
Classe,  1875,  S.  149. 


86  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

times  as  great  as  that  in  the  smaller  veins  of  the  head.  As,  during  such  an 
experiment,  the  blood  is  free  to  pass  from  the  aorta  through  one  carotid  and 
both  vertebra]  arteries  to  the  head,  and  to  return  through  all  the  veins  of 
that  part,  except  one  external  jugular,  to  the  vena  cava,  it  is  demonstrated 
that  there  must  be  a  continuous  flow  from  the  aorta,  through  the  capillaries 
of  the  head,  into  the  veins,  because  the  pressure  in  the  aorta  is  many  times  as 
greal  as  the  pressure  in  the  veins.  Obviously,  such  an  experiment,  although 
very  instructive,  gives  only  roughly  qualitative  results. 

Two  things  will  be  noted,  moreover,  in  such  an  experiment.  One  is  that 
the  venous  column  is  steady  ;  the  other  is  that  the  arterial  column  is  perpetu- 
ally fluctuating  in  a  rhythmic  manner.  The  top  of  the  arterial  column  shows 
a  regular  rise  and  fall  of  perhaps  a  few  centimeters,  the  rhythm  of  which  is 
the  same  as  that  of  the  breathing  of  the  animal  ;  and,  while  the  surface  is  thus 
rising  and  falling,  it  is  also  the  seat  of  frequent  flickering  fluctuations  of 
smaller  extent,  the  rhythm  of  which  is  regular,  and  agrees  with  that  of  the 
heart's  beat.  At  no  time,  however,  do  the  respiratory  fluctuations  of  the  arte- 
rial column  amount  to  more  than  a  fraction  of  its  mean  height;  compared  to 
which  last,  again,  the  cardiac  fluctuations  are  still  smaller.  It  is  clear,  then, 
that  the  aortic  pressure  changes  with  the  movements  of  the  chest,  and  with 
the  systoles  and  diastoles  of  the  left  ventricle.  But  stress  is  laid  at  present 
upon  the  fact  that  the  aortic  pressure  at  its  lowest  is  several  times  as  high  as 
the  pressure  in  the  smaller  veins  of  the  head.  Therefore,  the  occurrence  of 
incessant  fluctuations  in  the  aortic  pressure  cannot  prevent  the  continuous 
movement  of  the  blood  out  of  the  arteries,  through  the  capillaries,  into  the 
veins. 

The  upright  tubes  employed  in  the  foregoing  experiment  are  called  "  man- 
ometers." l  They  were  first  applied  to  the  measurement  of  the  arterial  and 
venous  blood-pre.-sures  by  a  clergyman  of  the  Church  of  England,  Stephen 
Hales,  rector  of  Farringdon  in  Hampshire,  who  experimented  with  them 
upon  the  horse  first,  and  afterward  upon  other  mammals.  He  published  his 
method  and  results  in  1 733.2  The  height  of  the  manometric  column  is  a 
true  measure  of  the  pressure  which  sustains  it;  for  the  force  derived  from 
gravity  with  which  the  bloml  in  the  tube  presses  downward  at  its  lower  open- 
ing is  exactly  equal  to  the  force  with  which  the  blood  in  the  artery  or  vein  is 
pressed  upward  at  the  same  opening.  The  downward  force  exerted  by  the 
column  of  blood  varies  direct  ly  with  the  height  of  the  column,  but,  by  the  laws 
of  fluid  pressure,  does  not  vary  with  the  calibre  of  the  manometer,  which  cali- 
bre may  therefore  be  settled  on  other  grounds.  It  follows  also  that  the  arterial 
and  venous  manometers  need  not  be  of  the  same  calibre.  Were,  however, 
another  fluid  than  the  blood  it-elf  used  in  the  manometer  to  measure  a  given 
intravascular  pressure,  a-  is  easily  possible,  the  height  of  the  column  would 
differ  from   that  of  the  column  of  blood.      For  a  given  pressure   the  height 

1  From  iKirnr.  rare.  The  Dame  was  given  from  such  tubes  being  used  to  measure  the  tension 
of  gases. 

2  Stephen  Hales  :  Statical  Essays :  containing  Hcema&taticks,  etc.,  London,  1733,  vol.  ii.  p.  1. 


CIRCULATION. 


87 


of  the  column  is  inverse  to  the 
density  of  the  manometric  fluid. 
For  example,  a  given  pressure  will 
sustain  a  far  taller  column  of  blood 
than  of  mercury. 

The  Mercurial  Manometer. — 
The  method  of  Hales,  in  its  orig- 
inal simplicity,  is  valuable  from 
that  very  simplicity  for  demonstra- 
tion, but  not  for  research.  The 
clotting  of  the  blood  soon  ends  the 
experiment,  and,  while  it  continues, 
the  tallness  of  the  tube  required  for 
the  artery,  and  the  height  of  the 
column  of  blood,  are  very  incon- 
venient. It  is  essential  to  under- 
stand next  the  principles  of  the 
more  exact  instruments  employed 
in  the  modern  laboratory. 

In  1828  the  French  physician 
and  physiologist  J.  L.  M.  Poiseuillc 
devised  means  both  of  keeping  the 
blood  from  clotting  in  the  tubes, 
and  of  using  as  a  measuring  fluid 
the  heavy  mercury  instead  of  the 
much  lighter  blood.  He  thereby 
secured  a  long  observation,  a  low 
column,  and  a  manageable  man- 
ometer.1 The  "  mercurial  man- 
ometer" of  to-day  is  that  of  Poi- 
seuille,  though  modified  (see  Fig. 
15).  In  an  improved  form  it  con- 
sists of  a  glass  tube  open  at  both 
ends,  and  bent  upon  itself  to  the 
shape  of  the  letter  U.  'Phis  is  held 
upright  by  an  iron  frame.  If  mer- 
cury be  poured  into  one  branch  of 
the  U,  it  will  fill  both  branches  to 
an  equal  height.  If  fluid  be  driven 
down  upon  the  mercury  in  one 
branch  or  "limb"  of  the  tube,  it 
will  drive  some  of  the  mercury  out 
of  that  limb  into  the  other,  ami  the 
rest  at  very  unequal  levels.  The  di 
1  J.  L.  M.  Poiseuille:  Becherches 


Fig.  15. — Diagram  of  the  recording  mercurial  man- 
ometer and  the  kymograph;  the  mercury  Is  indicated  in 
deep  black  :  M,  the  manometer,  connected  by  the  leaden 
pipe,  L,  with  a  glass  cannula  tied  into  the  proximal 
stump  of  the  left  common  carotid  artery  of  a  dog;  A, 
the  aorta;  C,  the  stop-cock,  hy  opening  which  the  man- 
ometer maybe  made  to  communicate  through  RT,  the 
rubher  tube,  with  ;i  pressure  bottle  of  solution  of  sodium 
carbonate;  F,  the  float  of  ivory  and  hard  rubber;  R,  the 
lighl  Bteel  rod,  kept  perpendicular  bj  B,  the  steel  bear- 
ing; /'.  the  glass  capillary  pen  charged  w  ith  quieklydry- 
ing  ink  ;  T,  a  thread  which  is  caused,  bj  the  weight  of  a 
light  ring  of  metal  suspended  from  it,  to  press  the  pen 
obliquely  and  gently  agalnsl  the  paper  with  which  la 
covered  /'.  the  brass  "  drum  "  of  the  kj  mograph,  «  hicb 
drum  revolves  in  the  direction  of  the  arrow.  The  Bup 
ports  of  the  manometer  and  the  body  and  clock-work 
of  the  kymograph  are  omitted  for  the  sake  of  simplicity. 
The  aorta  and  its  brandies  are  draw  n  disproportionately 
large  for  the  sake  of  clearness. 

two  surfaces  of  the  mercury  may  come  to 
fference  of  level,  expressed  in  millimeters, 
sur  la  force  du  cceut  aortique,  Paris,  1828. 


88  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

measures  the  height  of  the  manometric  column  of  mercury  the  downward  pres- 
sure of  which  in  one  limb  of  the  tube  is  just  equal  to  the  downward  pressure 
of  the  fluid  in  the  other.  In  order  to  adapt  this  "  U-tube"  to  the  study  of  the 
blood-pressure,  that  limb  of  the  tube  which  is  to  communicate  with  the  artery 
or  vein  is  capped  with  a  cock  which  can  be  closed.  Into  this  same  limb,  a  little 
way  below  the  cock,  opens  at  right  angles  a  short  straight  glass  tube,  which  is 
to  communicate  with  the  blood-vessel  through  a  long  flexible  tube  of  lead,  sup- 
ported by  the  iron  frame,  and  a  short  glass  cannula  tied  into  the  blood-vessel 
itself.  Two  short  pieces  of  india-rubber  tube  join  the  lead  tube  to  the  manometer 
and  the  cannula.  Before  the  blood-vessel  is  connected  with  the  manometer,  the 
Latter  i-  tilled  with  fluid  between  the  surface  of  the  mercury  next  the  blood- 
vessel and  the  outer  end  of  the  lead  tube,  which  fluid  is  such  that  when  mixed 
witli  blood  it  prevents  or  greatly  retards  coagulation.  With  this  same  fluid 
the  glass  cannula  in  the  blood-vessel  is  also  filled,  and  then  this  cannula  and 
the  lead  tube  are  connected.  The  cock  at  the  upper  end  of  the  "  proximal 
limb"  of  the  manometer  is  to  facilitate  this  filling,  being  connected  by  a  rub- 
ber tube  with  a  "pressure  bottle,"  and  is  closed  when  the  filling  has  been 
accomplished.  The  fluid  introduced  by  Poiseuille  and  still  generally  used  is 
a  strong  watery  solution  of  sodium  carbonate.  A  solution  of  magnesium  sul- 
phate is  also  good.  If,  in  injecting  this  fluid,  the  column  of  mercury  in  the 
"  distal  limb"  is  brought  to  about  the  height  which  is  expected  to  indicate  the 
blood-pressure,  but  little  blood  will  escape  from  the  blood-vessel  when  the 
clamp  is  taken  from   it,  and  coagulation   may  not  set  in  for  a  long  time. 

The  Recording  Mercurial  Manometer  and  the  Graphic  Method. — 
When  the  arterial  pressure  is  under  observation,  the  combined  respiratory 
and  cardiac  fluctuations  of  the  mercurial  column  are  so  complex  and  fre- 
quent  that  it  is  very  hard  to  read  off  their  course  accurately  even  with  the 
help  of  a  millimeter-scale  placed  beside  the  tube.  In  1847  this  difficulty  led 
the  German  physiologist  Carl  Ludwig  to  convert  the  mercurial  manometer 
into  a  self-registering  instrument.  This  invention  marked  an  epoch  not 
merely  in  the  investigation  of  the  circulation,  but  in  the  whole  science  of 
physiology,  by  beginning  the  present  "graphic  method"  of  physiological 
work,  which  has  led  to  an  immense  advance  of  knowledge  in  many  depart- 
ments. Ludwig  devised  the  "recording  manometer"  by  placing  upon  the 
mercury  in  the  distal  air-containing  limb  of  Poiseuille's  instrument  an  ivory 
float,  bearing  a  light,  stiff,  vertical  rod  (see  Fig.  15).  Any  fluctuation  of  the 
mercurial  column  caused  float  and  rod  to  rise  and  fall  like  a  piston.  The  rod 
projected  well  above  the  manometer,  at  the  mouth  of  which  a  delicate  bear- 
in-  was  provided  to  keep  the  motion  of  the  rod  vertical.  A  very  delicate 
pen  placed  horizontally  was  fastened  at  right  angles  to  the  upper  end  of  the 
rod.  If  a  firm  vertical  surface,  covered  with  paper,  were  now  placed  lightly 
in  contact  with  the  pen,  a  rise  of  the  mercury  would  cause  a  corresponding 
vertical  line  to  be  marked  upon  the  paper,  and  a  succeeding  fall  would 
cause  the  descending  pen  to  inscribe  a  second  line  covering  the  first.  If 
now  the  vertical  surface  were  made  to  move  past  the  pen  at  a  uniform  rate, 


CIBCULA  TION.  8 1 » 

the  successive  up-and-down  movements  of  the  mercury  would  no  longer  be 
marked  over  and  over  again  in  the  same  place  so  as  to  produce  a  single  ver- 
tical line.  The  space  and  time  taken  up  by  each  fluctuation  would  be  graph- 
ically recorded  in  the  form  of  a  curve,  itself  a  portion  of  a  continuous  trace 
marked  by  the  successive  fluctuations;  thus  both  the  respiratory  and  cardiac 
fluctuations  could  be  registered  throughout  an  observation  by  a  single  complex 
curviug  line.  Ludwig  stretched  his  paper  around  a  vertical  hollow  cylinder 
of  brass,  made  to  revolve  at  a  regular  known  rate  by  means  <>f  clock-work, 
and  the  conditions  above  indicated  were  satisfied  l  (see  Fig.  1 5).  Upon  the 
surface  of  such  a  cylinder  vertical  distance  represents  space,  and  a  vertical  line 
of  measurement  is  called,  by  au  application  of  the  language  of  mathematics, 
an  "ordinate;"  horizontal  distance  represents  time,  and  a  horizontal  line  of 
measurement  is  called  an  "  abscissa."  The  curve  marked  by  the  events  re- 
corded is  always  a  mixed  record  of  space  and  time.  The  instrument  itself, 
the  essential  part  of  which  is  the  regularly  revolving  cylinder,  is  called  the 
"  kymograph." 2  It  has  undergone  many  changes,  and  many  varieties  of  it 
are  in  use.  Any  motor  may  be  used  to  drive  the  cylinder,  provided  that  the 
speed  of  the  latter  be  uniform  and  suitable. 

The  curve  written  by  the  manometer  or  other  recording  instrument  may 
either  be  marked  upou  paper  with  ink,  as  in  Ludwig's  earliest  work  ;  or  may 
be  marked  with  a  needle  or  some  other  fine  pointed  thing  upon  paper  black- 


Fig.  16.-  The  trace  of  arterial  blood-pressure  from  a  dog  anaesthetized  with  morphia  and  ether.  The 
cannula  was  in  the  proximal  stump  of  the  common  carotid  artery.  The  curve  is  to  he  read  from  left 
to  right. 

/',  the  pressure  trace  written  by  the  recording  mercurial  manometer ; 

B  L,  the  base-line  or  abscissa,  representing  the  pressure  of  the  atmosphere.  The  distance  between 
the  base-line  and  the  pressure-curve  varies,  in  the  original  trace,  between  62  and  77  millimeters/there 
fore  the  pressure  varies  between  124  anil  154  millimeters  of  mercury,  less  a  small  correction  for  the 
weight  <>f  the  sodium-carhonate  solution  ; 

7",  the  time  trace,  made  up  of  intervals  of  two  seconds  each,  and  written  by  an  electro-mag- 
netlc  chronograph. 

ened  with  soot  over  n  flame.  The  trace  written  upon  Bmoked  paper  is  the 
more  delicate.  After  the  trace  has  been  written,  the  Bmoked  paper  is  removed 
from  the  kymograph  and   passed  through  a  pan  of  shellac  varnish.     This 

1  C.  Ludwig:  "Beitrage  zur  Kenntnisa  dea  Einflusaea  der  Reapirationabewegungen  auf 
den  Blutlauf  ini  Aortenaysteme,"  Miiller'a  Archiv  fiir  Anatomic,  Physiologic,  vmd  wmenschqflliche 
Mediem,  etc.,  1847,  S.  242.  2  From  KVfta,  a  wave. 


90  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

when  dry  fixes  the  trace,  which   thereafter  will  not  be  spoiled  by  handling. 

In  Figure  16  the  uppermost  line  shows  a  trace  which  fairly  represents  the 
successive  fluctuations  of  the  aortic  pressure  of  the  dog.  The  longer  and 
ampler  fluctuations  are  respiratory,  the  briefer  and  slighter  are  cardiac,  in 
each  respiratory  curve  the  lowest  point  and  the  succeeding  ascent  coincide  with 
Inspiration  ;  the  highest    point  and   the  succeeding  descent   with   expiration. 

The  horizontal  middle  line  is  the  base  line,  representing  the  pressure  of  the 
atmosphere.  The  base-lirje  ha-  been  shitted  upward  in  the  figure  simply  in 
order  to  save  room  on  the  page.  In  the  lowermost  line  the  successive  spaees 
from  left  to  right  of  the  read.r  represenl  successive  intervals  of  time  of  two 
seconds  each,  written  by  an  electro-magnetic  chronograph.  The  pressure-trace 
taken  from  a  vein  may  in  certain  regions  near  the  chest  show  respiratory  fluc- 
tuations, l>nt  nowhere  cardiac  ones,  as  the  pulse  is  not  transmitted  to  the  veins. 
The  venous  pressure  i>  so  small,  that  for  the  practical  study  of  it  a  recording 
manometer  must  he  used  in  which  some  lighter  fluid  replaces  the  mercury, 
which  would  give  a  column  of  insufficient  height  for  working  purposes.  The 
values  obtained  are  then  reduced  by  calculation  to  millimeters  of  mercury,  for 
comparison  with  the  arterial  pressure.  The  intravascular  pressure  at  a  given 
moment  can  he  measured  by  measuring  a  vertical  line  or  "ordinate"  drawn 
from  the  curve  written  by  the  manometer  to  the  horizontal  base-line.  The 
latter  represents  the  height  of  the  manometric  column  when  just  disconnected 
from  the  blood-vessel  ;  that  is,  when  acted  upon  only  by  the  weight  of  the 
atmosphere  and  of  the  solution  of  sodium  carbonate.  To  ascertain  the  blood- 
pressure,  the  length  of  the  Hue  thus  measured  must  be  doubled;  because  the 
mercury  in  the  proximal  limb  of  the  manometer  sinks  under  the  blood-pres- 
sure exactly  as  much  as  the  float  rises  in  the  distal  limb.  A  small  correction 
must  also  be  made  for  the  weight  of  the  solution  of  sodium  carbonate. 

The  Mean  Pressure. — The  "mean  pressure"  is  the  average  pressure  dur- 
ing whatever  length  of  time  the  observer  chooses.  The  mean  pressure  for  the 
given  time  is  ascertained  from  the  manometric  trace  by  measurements  too 
complicated  to  be  explained  here.  As  the  weight  and  consequent  inertia  of 
the  mercury  cause  it  to  fluctuate  according  to  circumstances  more  or  less  than 
the  pressure,  the  mean  pressure  is  much  more  accurately  obtained  from  the 
mercurial  manometer  than  is  the  true  height  of  each  fluctuation,  which  is  very 
commonly  written  too  small.  Therefore,  it  is  especially  the  mean  pressure 
that  is  studied  by  means  of  the  mercurial  manometer.  The  true  extent  and 
finer  characters  of  the  -ingle  fluctuations  caused  by  the  heart's  beat  are  better 
studied  with  other  instruments,  as  we  shall  see  in  dealing  with  the  pulse. 

It  has  been  seen  that  the  blood  (low-  continuously  through  the  capillaries 
because  the  pressure  is  continually  high  in  the  arteries  and  low  in  the  veins. 
The  reader  is  now  in  position  to  understand  statements  of  the  blood-pressure 
expressed  in  millimeters  of  mercury.  The  mean  aortic  pressure  in  the  dog  is 
far  from  being  always  the  same  even  in  the  same  animal.  W  v  have  found  it, 
in  the  ease  referred  to  on  page  85,  to  be  equivalent  to  about  121  millimeters 
of  mercury.     It  will  very  commonly  be  found  higher  than  this,  and  may  range 


CIRCULATION.  91 

up  to,  or  above,  200  millimeters.  In  man  it  i>  probably  higher  than  in  the 
dog.  The  pressure  in  the  other  arteries  derived  from  the  aorta  which  have 
been  studied  manoinetricalry  is  not  very  greatly  lower  than  in  that  vessel.  In 
the  pulmonary  arteries  the  pressure  is  probably  much  lower  than  in  the  aortic 
system.  The  pressure  in  the  small  veins  of  the  head  of  the  dog,  the  cannula 
being  in  the  distal  stump  of  the  external  jugular  vein,  we  have  found  already 
in  one  case  to  equal  about  14  millimeters  of  mercury.  In  such  a  case  the 
presence  of  valves  in  the  veins  and  other  elements  of  difficulty  make  the 
mean  pressure  hard  to  obtain  as  opposed  to  the  maximum  pressure  during 
the  period  of  observation. 

If  a  cannula  be  so  inserted  as  to  transmit  the  pressure  obtaining  within 
the  great  veins  of  the  neck  just  at  the  entrance  of  the  chest,  without  interfer- 
ing with  the  movement  of  the  blood  through  them,  and  if  a  manometer  be 
connected  with  this  cannula,  the  fluid  will  fall  below  the  zero-point  in  the 
distal  limb,  indicating  a  slight  suction  from  within  the  vein,  and  thus  a 
slightly  "  negative  "  pressure.1  This  negative  pressure  may  sometimes  become 
more  pronounced  during  inspiration  and  regain  its  former  value  during  ex- 
piration. Sometimes,  again,  the  pressure  during  expiration  may  become  posi- 
tive. The  continuous  flow  from  the  great  arteries  through  the  capillaries  to 
the  veins,  and  through  these  to  the  auricle,  is  therefore  shown  by  careful 
quantitative  methods,  no  less  than  by  the  tube  of  Hales,  to  be  simply  a 
case  of  movement  of  a  fluid  from  seats  of  high  to  seats  of  lower  pressure. 

The  Symptoms  of  Bleeding-  in  Relation  to  Blood-pressure. — The  dif- 
ferences of  pressure  revealed  scientifically  by  the  manometer  exhibit  them- 
selves in  a  very  important  practical  way  when  blood-vessels  are  wounded  and 
bleeding  occurs.  If  an  artery  be  cleanly  cut,  the  high  pressure  within  drives 
out  the  blood  in  a  long  jet,  the  length  of  which  varies  rhythmically  with  the 
cardiac  pulse,  but  varies  only  to  a  moderate  degree.  From  wounded  capil- 
laries, or  from  a  wounded  vein,  owing  to  the  low  pressure,  the  blood  does  not 
spring  in  a  jet,  but  simply  flows  out  over  the  surface  and  drips  away  without 
pulsation.  At  the  root  of  the  neck,  where  the  venous  pressure  may  rhythmi- 
cally fall  below  and  rise  above  the  atmospheric  pressure,  the  bleeding  from 
a  wounded  vein  may  be  intermittent. 

D.  The  Causes  of  the  Pressure  in  the  Arteries,  Capillaries, 

and  Veins. 

The  causes  of  the  continuous  high  pressure  in  the  arteries  musl  first  engage 
our  attention. 

Resistance. — The  great  ramification  of  the  arterial  system  at  a  distance 
from  the  heart  culminates  in  the  formation  of  the  countless  arterioles  mi  the 
confines  of  the  capillary  system.  We  have  already  seen  direct  evidence  of  the 
friction  in  the  minute  vessels  which  results  from  this  enormous  subdivision  of 
the  blood-path.     The  force  resulting  from   this   friction   i-  propagated   back- 

1  II.  Jacobson :  "  Ueber  die  Blutbewegung  in  den  Venen,"  Reicherts  •"<</  </"  Boie-iJey- 
mond's  Arckiv  fur  Anatomic,  Phyziologie,  etc.,  1867,  8.  224. 


92  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

ward  according  to  the  laws  of  fluid  pressure,  and  constitutes  a  strong  resist- 
ance to  the  onward  movement  of  the  blood  out  of  the  heart  itself.  Friction 
is  everywhere  present  in  the  vessels,  but  is  greatest  in  the  very  small  ones 
collectively. 

Power. — Where  the  aorta  springs  from  the  heart,  the  rhythmic  contrac- 
tions of  the  left  ventricle  force  open  the  arterial  valve,  and  force  intermittent 
charges  of  blood  into  the  arterial  system,  overcoming  thus  the  opposing  force 
derived  from  friction.  The  wall  of  the  arterial  system  is  very  elastic  every- 
where. Thus  the  high  pressure  in  the  arteries  results  from  the  interaction  of 
the  power  derived  from  the  heart's  beat  and  the  resistance  derived  from  fric- 
tion. That  the  high  pressure  is  continuous  depends  upon  the  capacity  for 
distention  possessed  by  the  elastic  arterial  wall. 

Balance  of  the  Factors  of  the  Arterial  Pressure. — In  order  to 
study  the  causation  of  the  arterial  pressure,  let  us  imagine  that  it  has  for  some 
reason  sunk  very  low;  but  that,  at  the  moment  of  observation,  a  normally 
beating  heart  is  injecting  a  normal  blood-charge  into  the  aorta.  The  first 
injection  would  find  the  resistance  of  friction  present,  and  the  elastic  arterial 
wall  but  little  distended.  For  this  injection  some  room  would  be  made  by 
the  displacement  of  blood  into  the  capillaries.  But  it  would  be  easier  for  the 
arterial  wall  to  yield  than  for  the  friction  to  be  overcome,  so  the  injected 
blood  would  largely  be  stored  within  the  arterial  system  and  thus  raise  the 
pressure.  Succeeding  injections  would  have  similar  results;  it  would  continue 
to  be  easier  for  the  injected  blood  to  distend  the  arteries  than  to  escape  from 
them;  and  the  arterial  pressure  would  rise  rapidly  toward  its  normal  height. 
Presently,  however,  a  limit  would  be  reached;  a  time  would  come  when  the 
elastic  wall,  already  well  stretched,  would  have  become  tenser  and  stiffer  and 
would  yield  less  readily  before  the  entering  blood  ;  and  now  a  larger  part 
than  before  of  each  successive  charge  of  blood  would  be  accommodated 
by  the  displacement  of  an  equivalent  quantity  into  the  capillaries,  and  a  smaller 
part  by  the  yielding  of  the  arterial  wall.  Normal  conditions  of  pressure 
would  lie  reached  and  maintained  when  the  blood  accommodated,  during  each 
systole  of  the  ventricle,  by  the  yielding  of  the  arterial  wall  should  exactly 
equal  in  amount  tin.'  blood  discharged  from  the  arteries  into  the  capillaries 
during  each  ventricular  diastole;  for  then  the  quantity  of  blood  parted  with 
by  the  arteries  during  both  the  systole  and  the  diastole  of  the  heart  would 
be  exactly  the  same  as  that  received  during  its  systole  alone. 

We  see  that,  at  each  cardiac  systole,  the  cardiac  muscle  does  work  in  main- 
taining the  capillary  flow  againsl  friction,  and  also  does  work  upon  the  arte- 
rial wall  in  expanding  it.  A  portion  of  the  manifest  energy  of  the  heart's 
beal  thus  becomes  potential  in  the  stretched  elastic  fibres  of  the  artery.  The 
moment  that  the  work  of  expansion  ceases,  the  stretched  elastic  fibres  recoil; 
their  potential  energy,  just  received  from  the  heart,  becomes  manifest,  and 
work  is  done  in  maintaining  the  capillary  flow  against  friction  during  the 
repose  of  the  cardiac  muscle.  At  the  beginning  of  this  repose  the  arterial 
valves  have  been  closed  by  the  arterial  recoil.      When,  at  each  cardiac  systole, 


CIRCULATION.  93 

the  arterial  wall  expands  before  the  entering  blood,  the  pressure  rises,  for 
more  blood  is  entering  the  arterial  system  than  is  leaving  it  ;  when,  at  each 
cardiac  diastole,  the  arterial  wall  recoils,  the  pressure  fall-,  for  blood  i>  having 
the  arterial  system,  and  none  is  entering  it.  But  before  the  fall  has  had  time 
to  become  pronounced,  while  the  arterial  pressure  is  still  high,  the  cardiac  sys- 
tole recurs,  and  the  pressure  rises  again,  as  at  the  preceding  fluctuation. 

The  Arterial  Pulse. — The  increased  arterial  pressure  and  amplitude  at 
the  cardiac  systole,  followed  by  diminished  pressure  and  amplitude  at  the 
cardiac  diastole,  constitute  the  main  phenomena  of  the  arterial  pulse.  They 
are  marked  in  the  manoinet rie  trace  by  those  lesser  rhythmic  fluctuations  of 
the  mercury  which  correspond  with  the  heart-beats.  The  causes  of*  the  arte- 
rial pulse  have  just  been  indicated  in  dealing  with  the  causes  of  the  arterial 
pressure.  The  pulse,  in  some  of  its  details,  will  be  studied  further  for  itself 
in  a  later  chapter.  For  the  sake  of  simplicity,  the  respiratory  fluctuations  of 
the  arterial  pressure  have  not  been  dealt  with  in  the  discussion  just  con- 
cluded. The  causes  of  these  important  fluctuations  are  very  complex  and  are 
treated  of  under  the  head  of  Respiration. 

The  arterial  pressure,  then,  results  from  the  volume  and  frequency  of  the 
injections  of  blood  made  by  the  heart's  contraction  ;  from  the  friction  in  the 
vessels;  and  from  the  elasticity  of  the  arterial  wall. 

The  Capillary  Pressure  and  its  Causes. — When  we  studied  the  move- 
ment of  the  blood  in  the  capillaries,  we  found  the  pressure  in  them  to  be  low 
and  free  from  rhythmic  fluctuations.  In  both  of  these  qualities  the  capillary 
pressure  is  in  sharp  contrast  with  the  arterial.  What  is  the  reason  of  the  differ- 
ence? The  work  of  driving  the  blood  through  as  well  as  into  the  capillaries  Is 
done  during  the  contraction  of  the  heart's  wall  by  its  kinetic  energy.  During 
the  repose  of  the  heart's  wall  and  the  arterial  recoil  this  work  is  continued  by 
kinetic  energy  derived,  as  we  have  seen,  from  the  preceding  cardiac  contraction. 
The  work  of  producing  the  capillary  flow  is  done  in  overcoming  the  resistance 
of  friction.  The  .capillary  walls  are  elastic.  The  same  three  factors,  then — 
the  power  of  the  heart,  the  resistance  of  friction,  the  elasticity  of  the  wall — 
which  produce  the  arterial  pressure  produce  the  capillary  pressure  also.  Why 
is  the  capillary  pressure  normally  low  and  pulseless?  The  answer  is  not 
difficult.  The  friction  which  must  be  overcome  in  order  t<>  propel  the  blood 
out  of  the  capillaries  into  the  wider  venous  branches  is  only  a  part  of  the  total 
friction  which  opposes  the  admission  of  the  blood  to  the  minuter  vessels.  The 
resistance  is  therefore  diminished  which  the  blood  ha-  yet  to  encounter  after 
it  has  actually  entered  the  capillaries.  The  force  which  propels  the  blood 
through  the  capillaries,  although  amply  sufficient,  is  greatl}  less  than  the 
force  which  propels  it  into  and  through  the  larger  arteries.  In  both 
cases  alike  the  force  is  that  of  the  heart'-  heat.  But,  in  overcoming  the 
friction  which  resists  the  entrance  of  the  blood  into  the  capillaries,  a  large 
amount  of  the  kinetic  energy  derived  from  the  heart  has  become  converted 
into  heat.  The  power  is  therefore  diminished.  As,  in  producing  the  high 
arterial  pressure,  much  power  is  met  by  much    resistance,  and   the  elastic  wall 


94  . I  X    . l  MER TCA  X    TEXT- H 0 0 K    0 F  PHYSIOL OGT. 

is,  therefore,  distended  with  accumulated  blood;  so,  in  producing  the  low  capil- 
lary pressure,  diminished  power  is  met  by  diminished  resistance,  outflow  is 
relatively  easy,  accumulation  is  slight,  and  the  elasticity  of  the  delicate  wall 
is   1  hi t    little  called   upon. 

The  Extinction  of  the  Arterial  Pulse. — But  why  is  the  capillary  pres- 
sure pulseless, as  the  microscope  shows?  To  explain  this,  no  new  factors  need 
discussion,  Imt  only  the  adjustment  of  the  arterial  elasticity  to  the  intermittent 
injections  from  the  heart  and  to  the  total  friction  which  opposes  the  admission 
of  blood  to  the  capillaries.  This  adjustment  is  such  that  the  recoil  of  the 
arteries  displaces  blood  into  the  capillaries  during  the  ventricular  diastole  at 
exactly  the  same  rate  as  that  produced  by  the  ventricular  contraction  during 
the  ventricular  systole.  Thus,  through  the  elasticity  of  the  arteries,  the  car- 
diac pulse  undergoes  extinction  ;  and  this  becomes  complete  at  the  confines 
of  the  capillaries.  The  respiratory  fluctuations  become  extinguished  also,  and 
the  movement  of  the  blood  in  the  capillaries  exhibits  no  rhythmic  changes. 
This  conversion  of  an  intermittent  How  into  one  not  merely  continuous  but 
approximately  constant  affords  a  constant  blood-supply  to  the  tissues,  at  the 
same  time  that  the  cardiac  muscle  can  have  its  diastolic  repose,  and  the  ven- 
tricular cavities  the  necessary  opportunities  to  receive  from  the  veins  the 
blood    which   is  to  be  transferred  to  the  arteries. 

A  simple  experiment  will  illustrate  the  foregoing.  Let  a  long  india-rubber 
tube  be  taken,  the  wall  of  which  is  thin  and  very  elastic.  Tie  into  one  end 
of  the  tube  a  short  bit  of  glass  tubing  ending  in  a  fine  nozzle,  the  friction  at 
which  will  cause  great  resistance  to  any  outflow  through  it.  Tie  into  the 
other  end  of  the  rubber  tube  an  ordinary  syringe-bulb  of  india-rubber,  with 
valves.  Expel  the  air,  and  inject  water  into  the  tube  from  the  valved  bulb 
by  alternately  squeezing  the  latter  and  allowing  it  to  expand  and  be  filled 
from  a  basin.  The  rubber  tube  will  swell  and  pulsate,  but  if  its  elasticity 
have  the  right  relation  to  the  size  of  the  fine  glass  nozzle  and  to  the  amplitude 
and  frequency  of  the  strokes  of  the  syringe,  a  continuous  and  uniform  jet  will 
be  delivered  from  the  nozzle,  while  the  injections  of  water  will,  of  course,  be 
intermittent. 

The  Venous  Pressure  and  its  Causes. — The  pressure  in  the  peripheral 
veins  is  less  than  in  the  capillaries  and  declines  as  the  blood  reaches  the  larger 
vein-.  Very  close  to  the  chest  the  pressure  is  below  the  pressure  of  the 
atmosphere,  and  may  sometimes  vary  from  negative  to  positive,  following  the 
rhythm  of  the  breathing.  These  respiratory  fluctuations  will  be  considered  later. 
The  low  and  declining  pressures  under  which  the  blood  moves  through  the 
venules  and  the  larger  vein-  are  due  to  the  same  causes  as  those  which  account 
for  the  capillary  pressure.  It  is  -till  the  force  generated  by  the  heart's  con- 
tractions, and  made  uniform  by  the  elastic  arteries,  which  drives  the  blood 
into  and  through  the  veins  back  to  the  very  heart  itself.  As  the  blood  moves 
through  the  vein-,  what  resistance  it  encounters  is  still  that  of  the  friction 
ahead.  But  the  friction  ahead  is  progressively  less;  the  conversion  of  kinetic 
energy  into  heat   is  progressively  greater.     The  venous  wall  possesses  elas- 


CIRCULATION.  95 

ticity,  but  this  is  even  less  called  upon  than  that  of  the  capillaries;  and,  pres- 
ently, in  the  larger  veins,  the  moving  blood  is  found  to  press  no  harder  from 
within  than  the  atmosphere  from  without. 

Subsidiary  Forces  which  Assist  the  Flow  in  the  Veins. — There  are 
certain  forces  which,  occasionally  or  regularly,  assisl  the  heart  to  return  the 
venous  blood  into  itself.  Too  much  stress  is  often  laid  upon  these;  for  it  is 
easy  to  see  by  experiment  that  the  heart  can  maintain  the  circulation  wholly 
without  help.  The  origins  of  these  subsidiary  forces  arc  first,  the  contraction 
of  the  skeletal  muscles  in  general ;  second,  the  continuous  traction  of  the 
lungs;  third,  the  contraction  of  the  muscles  of  inspiration. 

The  Skeletal  Muscles  and  the  Venous  Valves. — A  vein  may  lie  in 
such  relation  to  a  muscle  that  when  the  latter  contracts  the  vein  is  pressed 
upon,  its  feeble  blood-pressure  is  overborne,  the  vein  is  narrowed,  and  blood 
is  squeezed  out  of  it.  The  veins  in  many  parts  are  rich  in  valves,  competent 
to  prevent  regurgitation  of  the  blood  while  permitting  its  How  in  the  physio- 
logical direction.  The  pressure  of  a  contracting  muscle,  therefore,  can  only 
squeeze  blood  out  of  a  vein  toward  the  heart,  never  in  the  reverse  direction. 
Muscular  contraction,  then,  may,  and  often  does,  assist  in  the  return  of  the 
venous  blood  with  a  force  not  even  indirectly  derived  from  the  heart.  But 
such  assistance,  although  it  may  be  vigorous  and  at  times  important,  is  tran- 
sient and  irregular.  Indeed,  were  a  given  muscle  to  remain  long  in  contrac- 
tion, the  continued  squeezing  of  the  vein  would  be  an  obstruction  to  the  flow 
through  it. 

The  Continuous  Pull  of  the  Elastic  Lungs. — The  influence  of  thoracic 
aspiration  upon  the  movement  of  the  blood  in  the  veins  deserves  a  fuller  dis- 
cussion. The  root  of  the  neck  is  the  region  where  this  influence  shows  itself 
most  clearly,  but  it  may  also  he  verified  in  the  ascending  vena  cava  of  an 
animal  in  which  the  abdomen  has  been  opened.  The  physiology  of  respira- 
tion shows  that  not  only  in  inspiration,  but  also  in  expiration,  the  elastic  til >i<  - 
of  the  lungs  are  upon  the  stretch,  and  are  pulling  upon  the  ribs  and  intercostal 
spaces,  upon  the  diaphragm,  and  upon  the  heart  and  the  great  vessels.  This 
dilating  force  at  all  times  exerted  upon  the  heart  by  the  lungs  is  of  assistance, 
as  we  shall  see,  in  the  diastolic  expansion  of  its  ventricles.  In  the  same  way 
the  elastic  pull  of  the  lung-  acts  upOD  the  vena-  cava'  within  the  chest,  and 
generates  within  them,  as  well  as  within  the  right  auricle,  a  force  of  suction. 
The  effects  upon  the  venous  flow  of  this  continuous  aspiration  are  besl  known 
in  the  system  of  the  descending  vena  cava.  This  suction  from  within  the 
chest  extends  to  the  great  veins  just  without  it  in  the  neck.  In  these,  close  t<> 
the  chest,  as  we  have  seen,  manometric  observation  reveals  :i  continuous  slight  ly 
negative  pressure.  A  little  farther  from  the  chest,  however,  hut  -till  within 
the  lower  portions  of  the  neck,  the  intravenous  pressure  is  slightly  positive. 
The  elastic  pull  of  the  lung,  therefore,  continuously  assists  in  unloading  the 
terminal  part  of  the  venous  system,  and  thus  differs  markedly  from  the  irreg- 
ular contractions  of  the  skeletal  muscles. 

The   Contraction  of  the  Muscles  of  Inspiration. —  But    some  skeletal 


96  AN  AMERICAN    TENT-BOOK    OF  PHYSIOLOGY. 

muscles,  those  of  inspiration,  regularly  add  their  rhythmic  contractions  to  the 
continuous  pull  of  the  lungs,  to  reinforce  the  latter.  Each  time  that  the  chest 
expands  there  is  an  increased  tendency  for  blood  to  be  sucked  into  it  through 
the  veins.  At  the  beginning  of  each  expiration  this  increase  of  suction 
abruptly  ceases. 

The  Respiratory  Pulse  in  the  Veins  near  the  Chest,  and  its  Limita- 
tion.—  In  quiet  breathing  the  movements  of  the  chest-wall  produce  no  very 
conspicuous  effect.  W,  however,  deep  and  infrequent  breaths  be  taken,  the 
pro-ore  within  the  veins  close  to  the  chest  becomes  at  each  inspiration  much 
more  negative  than  before;  and  at  each  inspiration  the  area  of  negative 
pressure  may  extend  to  a  greater  distance  from  the  chest  along  the  veins  of 
the  neck,  and  perhaps  of  the  axilla.  As  the  venous  pressure  in  these  parts 
now  falls  as  the  chest  rises,  and  rises  as  the  chest  falls,  a  visible  venous  pulse 
presents  itself,  coinciding,  not  with  the  heart-beats,  but  with  the  breathing. 
At  each  inspiration  the  veins  diminish  in  size,  as  their  contents  are  sucked 
into  the  chest  faster  than  they  are  renewed.  At  each  expiration  the  veins  may 
be  seen  to  swell  under  the  pressure  of  the  blood  coming  from  the  periphery. 
If  the  movements  of  the  air  in  the  windpipe  be  mechanically  impeded, 
these  changes  in  the  veins  reach  their  highest  pitch;  for  then  the  muscles  of 
expiration  may  actually  compress  the  air  within  the  lungs,  and  produce  a 
positive  pressure  within  the  vena  cava  and  its  branches,  with  resistance  to  the 
return  of  venous  blood  during  expiration,  shown  by  the  swelling  of  the  veins. 
These  phenomena  are  suddenly  succeeded  by  suction,  and  by  collapse  and 
disappearance  of  the  veins,  as  inspiration  suddenly  recurs.  The  respirators 
venous  pulse,  when  it  occurs,  diminishes  progressively  and  rapidly  as  the 
veins  arc  observed  farther  and  farther  from  the  root  of  the  neck — a  fact 
which  results  from  the  ilaccidity  of  the  venous  wall.  Were  the  walls  of  the 
veins  rigid,  like  glass,  the  successive  inspirations  would  produce  obvious 
accelerations  of  the  How  throughout  the  whole  venous  system,  and  the  con- 
tractions of  the  muscles  of  inspiration  would  rank  higher  than  they  do  among 
the  causes  of  the  circulation.  In  fact,  the  walls  of  the  veins  are  very  soft 
and  thin.  li\  therefore,  near  the  chest,  the  pressure  of  the  blood  within  the 
vein-  -inks  below  that  of  the  atmosphere,  the  place  of  the  blood  sucked  into 
the  chest  is  filled  only  partly  by  a  heightened  flow  of  blood  from  the  periph- 
ery, l>nt  partly  also  by  the  soft  venous  wall,  which  promptly  sinks  under 
the  atmospheric  pressure.  This  is  shown  by  the  visible  flattening,  perhaps 
disappearance  from  view,  of  the  vein.  This  process  reduces  the  visible 
venous  pulse,  when'  it  occur-,  to  a  local  phenomenon;  for,  at  each  inspira- 
tion, the  promptly  resulting  shrinkage  of  all  the  affected  veins  together  is 
marly  equivalent  to  the  loss  of  volume  due  to  the  sucking  of  blood  into  the 
chest.  Therefore  the  How  in  the  more  peripheral  veins  remains  but  slightly 
affected,  and  the  pressure  within  them  continue-  to  be  positive  and  without 
a  visible  pulse.  During  expiration  the  swelling  of  the  veins  near  the  chest, 
the  return  of  positive  pressure  within  them,  may  be  simply  from  the  return 
of  the  ordinary  balance  of  forces  alter  the  effects  of  a  deep  inspiration  have 


CIRCULA  TION.  97 

disappeared.  But,  if  expiration  be  violent  and  much  impeded,  the  positive 
pressure  may  rise  much  above  the  normal.  Here  again,  however,  regurgita- 
tion will  meet  with  opposition  from  the  venous  valves,  though  the  flow  from 
the  periphery  may  be  much  impeded. 

The  "  Dangerous  Reg-ion,"  and  the  Entrance  of  Air  into  a  "Wounded 
Vein. — Quite  close  to  the  chest,  then,  the  normal  venous  pressure  is  always 
slightly  negative ;  and  in  deep  inspiration  it  may  become  more  so,  and  this 
condition  may  extend  farther  from  the  chest  along  the  neck  and  axilla,  through- 
out a  region  known  to  surgeons  as  "the  dangerous  region."  It  is  important 
to  understand  the  reason  for  this  expression.  It  has  already  been  mentioned 
that  the  wounding  of  a  vein  in  this  region  may  cause  intermittent  bleeding. 
It  now  will  easily  be  understood  that  such  bleeding  will  occur  onlv  when  the 
pressure  is  positive — that  is,  during  expiration.  During  deep  and  difficult 
breathing,  indeed,  the  venous  blood  may  spring  in  a  jet  during  expiration 
instead  of  merely  flowing  out,  and  may  wholly  cease  to  flow  during  inspira- 
tion. The  cessation  is  due,  of  course,  to  the  blood  being  sucked  into  the 
chest  past  the  wound  rather  than  pressed  out  of  it. 

It  is  not,  however,  the  risks  of  hemorrhage  that  have  earned  the  name  of 
"dangerous"  for  the  region  where  intermittent  bleeding  may  occur.  The 
danger  referred  to  is  of  the  entrance  of  air  into  the  wounded  vein  and  into  the 
heart, — an  accident  which  is  commonly  followed  by  immediate  death,  for 
reasons  not  here  to  be  discussed.  Very  close  to  the  chest,  where  the  venous 
pressure  is  continuously  negative  and  the  veins  are  so  bound  to  the  fasciae  that 
they  may  not  collapse,  this  danger  is  always  present.  Throughout  the  rest 
of  the . dangerous  region,  the  entrance  of  air  into  a  wounded  vein  will  take 
place  only  exceptionally.  In  quiet  breathing  the  venous  pressure  is  continu- 
ously positive  throughout  most  of  this  region;  and  then  a  wounded  vein  will 
merely  bleed.  It  is  only  in  deep  breathing  that  a  venous  pulse  becomes  vis- 
ible here,  and  that  the  venous  pressure  becomes  negative  in  inspiration.  Bu< 
even  in  forced  breathing  it  is  rare  for  a  wounded  vein  of  the  dangerous  region 
to  do  more  than  bleed.  The  cause  of  this  lies  in  the  flaccidity  of  the  venous 
wall.  At  each  expiration  the  blood  may  jet  from  the  wound;  but  at  the  fol- 
lowing deep  inspiration  the  weight  of  the  atmosphere  flattens  the  vein  so 
promptly  that  the  blood  is  followed  down  by  the  wounded  wall  and  no  air 
enters  at  the  opening.  It  is  only  when,  during  deep  breathing,  the  wounded 
wall  for  some  reason  cannot  collapse,  thai  the  main  part  of  the  "dangerous 
region  "  justifies  its  name.  Should  the  tissues  through  which  the  vein  runs 
have  been  stiffened  by  disease,  or  should  the  wall  of  the  vein  adhere  to  a 
tumor  which  a  surgeon  is  lifting  as  he  cuts  beneath  it,  in  either  case  the  vein 
will  have  become  practically  a  rigid  tube.  Should  it  be  wounded  during  a 
deep  inspiration,  blood  will  be  sucked  past  the  wound,  but  the  atmospheric 
pressure  will  fail  to  make  the  wall  collapse;  air  will  be  drawn  into  the  cut, 
and  blood  and  air  will  enter  the  heart  together,  probably  with  deadly  effect. 

Summary. —  It  appears   from  what  has  gone  before   that   the  elasticity  of 
the  lungs  and  the  contractions  of  the  muscles  of  inspiration  regularly  assist  in 

Vol.  I.— 7 


98  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

unloading  the  veins  in  the  immediate  neighborhood  of  the  heart,  and  so  remove 
some  pan  of  the  resistance  to  be  overcome  by  the  contractions  of  the  cardiac 
muscle.  When  we  come  to  the  detailed  study  of  the  heart  it  will  appear  also 
that  a  slight  force  of  suction  is  generated  by  the  heart  itself,  which  force  adds 
it-  effects  upon  the  flow  of  venous  blood  to  those  of  the  elasticity  of  the  lungs 
and  of  the  contraction  of  the  muscles  of  inspiration. 

It  must  here  be  repeated,  however,  that  the  heart  is  quite  competent  to 
maintain  the  circulation  unaided.  This  is  proven  as  follows:  If  in  an  anaes- 
thetized mammal  a  cannula  be  placed  in  the  windpipe,  the  chest  be  widely 
opened,  and  artificial  respiration  be  established,  the  circulation,  though  modi- 
fied, continues  to  be  effective.  By  the  opeuing  of  the  chest  its  aspiration  has 
been  ended,  and  can  no  longer  assist  in  the  venous  return.  If,  further,  the 
animal  be  drugged  in  such  a  manner  as  completely  to  paralyze  the  skeletal 
muscles  throughout  the  body,  their  contractions  can  exert  no  influence  upon 
the  venous  return;  yet  the  circulation  is  still  kept  up  by  the  heart,  unaided 
either  by  the  elasticity  of  the  lungs,  by  the  contractions  of  the  muscles  which 
produce  inspiration,  or  by  those  of  any  other  skeletal  muscles. 

E.  The   Speed   of  the  Blood  in  the  Arteries,  Capillaries, 

and  Veins. 

If  we  keep  as  our  text,  in  discussing  the  circulation,  the  character  of  the 
capillary  flow,  it  will  be  seen  that  we  have  now  accounted  for  the  facts  that 
the  capillary  How  is  toward  the  veins;  that  it  shows  much  friction;  that  it  is 
continuous,  pulseless,  and  under  low  pressure.  We  have  not  yet  accounted 
for  the  fact  that  it  is  slow.  We  must  now  do  so,  but  must  first  state  aud 
account  for  the  speed  of  the  blood  in  the  arteries  and  veins. 

The  Measurement  of  the  Blood-speed  in  Large  Vessels;  the  "  Strom- 
uhr." — The  speed  of  the  blood  in  the  larger  veins  and  arteries  must  be  meas- 
ured indirectly.  We  can  picture  to  ourselves  the  volume  of  blood  which  moves 
past  a  given  point  in  a  given  blood-vessel  in  one  second,  as  a  cylinder  of 
blood  having  the  same  diameter  as  the  interior  of  the  blood-vessel.  The 
length  of  this  cylinder  will  then  be  expressed  by  the  same  number  which  will 
express  the  velocity  with  which  a  particle  of  the  blood  would  pass  the  given 
point  in  one  second,  provided  that  this  velocity  be  uniform  and  be  the  same 
for  all  the  particles.  In  order,  then,  to  learn  the  average  speed  of  the  blood 
;it  .1  given  point  of  an  artery  or  vein  during  a  certain  number  of  seconds,  we 
have  only  to  measure  the  calibre  of  the  blood-vessel  and  the  quantity  of 
blood  which  passes  the  selected  point  during  the  period  of  observation. 
From  these  two  measurements  the  speed  can  be  obtained  by  calculation.  But 
these  two  measurements  are  not  quite  easy.  The  physical  properties  of  the 
blood-vessels,  especially  of  the  veins,  make  their  calibres  variable  and  hard 
to  estimate  justly  a-  affected  by  the  conditions  present  during  an  experiment. 
The  menus  adopted  for  measuring  the  quantity  of  blood  passing  a  point  in  a 
given  time  necessarily  alters  the  resistance  encountered  by  the  How,  and  so  of 
itself  affects    both    the   rate   of  flow   and    the   blood-pressure;  and,  with  the 


CIHCCLA  TIO.X. 


99 


Fig.  17.— Diagram  of  longitudinal  sec- 
tion of  Ludwig's  "Stromuhr."  The  ar- 
rows mark  the  direction  of  the  blood- 
stream. For  further  description  see  the 
text. 


latter,  the  calibre  of  the  vessel.  For  these  reasons  any  measurement  of 
the  average  speed  of  the  blood  by  the  above  method  is  only  approximately 
correct.  The  best  instrument  for  measuring 
the  quantity  of  blood  driven  past  a  point 
during  an  experiment  i-  the  so-called  "strom- 
uhr" or  "rheometer"  of  Ludwig,  a  longitu- 
dinal section  of  which  is  given  diagrammati- 
cal lv  in  Figure  17.1  This  is  essentially  a 
curved  tube  shaped  like  the  Greek  capital 
letter  £2.  Each  end  of  the  tube  is  tied  into 
one  of  the  two  stumps  (a  and  6)  of  the  divided 
vessel.  These  ends  of  the  tube  are  as  nearly 
as  possible  of  the  same  calibre  as  the  vessel 
selected.  Each  limb  of  the  tube  is  dilated 
into  a  bulb,  and  the  upper  part  of  the  tube, 
including  the  two  bulbs,  is  of  glass;  the  lower 
part  of  each  limb  is  of  metal.  At  the  top, 
between  the  bulbs,  is  an  opening  for  filling 
the  tubes,  which  can  easily  be  closed  when  not 
in  use.  Each  end  of  the  tube  is  filled  with 
defibrinated  blood  before  being  tied  into  the 
blood-vessel.       In  the  limb  of  the  tube  (B, 

(Fig.  17)  which  is  the  farther  from  the  heart  if  an  artery  be  used,  or  the 
nearer  to  the  heart  if  a  vein,  the  defibrinated  blood  is  made  to  fill  the  cavity 
up  to  the  top  of  the  bulb.  In  the  other  limb  (.1.  Fig.  17)  the  blood  fills  the 
tube  only  up  to  a  mark  (e,  Fig.  17)  near  the  bottom  of  the  bulb.  Through 
the  opening  between  the  bulbs  the  still  vacant  space,  which  includes  the  whole 
of  the  bulb  .1,  is  filled  with  oil,  all  air  being  excluded.  The  opining  i>  then 
closed.  If  now  the  clamps  lie  removed  from  the  blood-vessel,  the  blood  of  the 
animal  will  enter  the  tube  at  a  and  drive  before  it  the  contents  of  the  tube. 
Thus  defibrinated  blood  from  /,'  will  be  driven  into  the  distal  -lump  of  the 
vessel  at  b,  and  will  enter  the  circulation  of  the  animal.  Oil  will  at  the  same 
time  be  driven  over  from  .1  to  />.  The  bulb  .1  has  upon  it  two  marks,  d  and 
e,  one  near  the  top  of  it,  the  other  near  the  bottom.  The  instanl  when  the 
line  between  the  oil  and  the  advancing  blood  reaches  the  mark  near  the  top 
of  A  is  the  instant  when  a  volume  of  blood  equal  to  that  of  the  displaced  oil 
has  entered  A,  past  the  mark  near  the  bottom  of  it.  The  capacity  of  the  tube 
between  the  two  marks  is  accurately  known.  The  time  required  for  this 
space  to  be  filled  with  the  entering  blood  is  measured  by  the  observer.     The 

calibre  of  the  metal  tube  at  a  i-  accurately  known,  and  i-  ass d  i<>  lie  equal 

to  the  calibre  of  the  blood-vessel,  from  these  measurements  the  average 
speed  of  the   blood-stream   at    <t   is  calculated. 

'J.  Dogiel  :  "Die  Ausmesaung  der  stromenden  Blutvolumina,"  BericlUe  fiber  di*  Verhand- 
lungen  der  k.  saeksisehen  OeseUschaft  der  Wiwemchaften  su  Leipzig,  M<dh.-j>hy8V6cfo  < '/<<*.«■,  1867, 
S.  200. 


100  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

The  metallic  lower  parr  of  the  instrument,  which  includes  both  limbs  of 
the  tube,  is  completely  divided  horizontally  at  c.  The  two  parts  are  so  built, 
however,  as  to  be  maintained  in  water-tight  apposition.  This  arrangement 
permits  the  whole  upper  part  of  the  instrument,  including  the  glass  bulbs,  to 
be  rotated  suddenly  upon  the  lower,  so  that  the  bulb  B  may  correspond  with 
the  entrance  for  the  blood  at  a,  and  the  bulb  ^i  with  the  exit  for  the  blood  at 
b.  If  this  rotation  be  effected  at  the  instant  when  the  space  between  the  two 
mark-  on  A  has  been  tilled  with  blood,  the  bulb  B,  now  charged  with  oil, 
will  be  tilled  by  the  blood  which  enters  next,  and  the  first  charge  of  the  ani- 
mal's own  blood  will  make  its  exit  at  6.  Oil  will  now  pass  over  from  B  to 
A;  when  the  line  between  it  and  the  blood  which  is  leaving  A  has  just 
reached  the  lower  mark  on  J,  the  bulbs  are  turned  back  to  their  original 
position.  Thus,  by  repeated  rotations,  each  of  which  can  be  made  to  record 
upon  the  kymograph  the  instant  of  its  occurrence,  a  number  of  charges  of 
blood  can  be  received  and  transmitted  in  succession;  it  is  always  the  same 
space,  between  the  marks  on  .1,  which  is  used  for  measuring  the  charge;  and 
the  time  of  the  experiment  can  be  much  prolonged.  By  this  procedure  the 
errors  due  to  a  single  brief  observation  can  be  greatly  reduced.  Indeed,  the 
time  of  entrance  of  a  single  charge  of  blood  would  be  quite  too  short  to  give 
a  satisfactory  result. 

The  use  of  the  stromuhr  not  only  affords  necessary  data  for  the  calcu- 
lation of  the  average  speed  of  the  blood,  but  seeks  directly  to  measure  the 
volume  of  blood  delivered  in  a  given  time  by  an  artery  to  its  capillary  dis- 
trict. It  is  evident  that  this  volume  is  a  quantity  of  fundamental  importance 
in  the  physiology  of  the  circulation.  Could  we  ascertain  it,  by  direct  meas- 
urement or  by  calculation,  for  the  aorta  or  pulmonary  artery,  we  should  know 
at  once  the  volume  of  blood  delivered  to  the  capillaries  in  one  second,  and 
thus  the  time  taken  for  the  entire  blood  to  enter  either  those  of  the  lungs  or 
of  tin'  system  at  large.  By  this  knowledge,  many  important  problems  would 
be  advanced  toward  solution. 

The  Measurement  of  Rapid  Fluctuations  of  Speed. — The  stromuhr 
can  give  only  the  average  speed  of  the  blood  during  the  experiment.  To 
study  rapid  fluctuations  of  speed,  another  method  is  needed.  If,  in  a  large 
animal,  a  vessel,  best  an  artery,  be  laid  bare,  a  needle  may  be  thrust  into  it  at 
right  angles.  If  the  needle  be  left  to  itself,  the  end  which  projects  from  the 
artery  will  lie  deflected  toward  the  heart,  because  the  point  will  have  been 
deflected  toward  the  capillaries  by  the  blood-stream.  The  angle  of  deflection 
might  be  read  off,  could  a  graduated  semicircle  be  adjusted  to  the  needle.  If 
the  stream  be  arrested,  the  needle  returns  to  its  position  at  right  angles  to  the 
artery.  The  greater  the  velocity  of  the  stream,  the  greater  is  the  deflection  of 
the  needle.  If.  later,  the  same  needle  be  thrust  into  a  tube  of  rubber  through 
which  water  flows  at  known  ran-  of  -peed,  the  speed  corresponding  to  each 
angle  of  deflection  of  the  needle  may  be  determined.  If  the  needle  were 
made  to  mark  upon  a  kymograph,  variations  of  the  speed  would  be  recorded 
as  a  curve. 


CIRCULATION.  101 

An  instrument  based  on  the  principles  jus!  described  is  valuable  for  the 
study  of  rapid  changes  of  velocity.1  In  an  artery,  its  needle  oscillates  rhyth- 
mically, showing  that  there  the  speed  of  the  1)1 1  varies  during  each  beat  of 

the  heart,  being  greatly  accelerated  by  the  systole  of  the  ventricle,  and  retarded 

by  the  cessation  of  the  systole.  It  will  be  remembered  that  the  microscope 
directly  shows  faint  rhythmic  accelerations  in  the  minute  arteries  of  the  frog. 
In  the  veins  rhythmic  changes  of  speed  do  not  occur  except  near  the  heart 
from   respiratory  causes. 

The  Speed  of  the  Blood  in  the  Arteries. — The  stromuhr  shows  that  the 
speed  of  the  blood  is  liable  to  great  variations.  This  fact,  and  the  range  of 
speed  in  the  arteries,  are  fairly  exhibited  by  the  results  obtained  by  Dogiel 
from  the  common  carotid  artery  of  a  dog,  the  experiment  upon  which  lasted 
127  seconds.  During  this  time  six  observations  were  made  which  varied  in 
length  from  14  to  30  seconds  each.  For  one  of  these  periods  the  average 
speed  was  243  millimeters  in  one  second  ;  for  another  period,  520  millimeters. 
These  were  the  extremes  of  speed  noted  in  this  case.2  The  speed  in  the 
arteries  diminishes  toward  the  capillaries. 

The  Speed  of  the  Blood  in  the  Veins. — The  speed  in  a  vein  tends  to  be 
slower  than  that  in  an  artery  of  about  the  same  importance,  but  is  not  neces- 
sarily so.3     It  increases  from  the  capillaries  toward  the  heart. 

The  Speed  of  the  Blood  in  the  Capillaries. — The  rate  of  the  capillary 
flow  may  be  measured  directly  under  the  microscope.  Certain  physiologists 
have  also  observed  the  movement  of  the  blood  in  the  retinal  capillaries  of 
their  own  eyes,  and  have  measured  its  rate  there.'  Both  methods  show  that 
in  the  capillaries  the  speed  is  very  much  less  than  in  the  large  arteries  or  large 
veins.  In  the  capillaries  of  the  web  of  the  frog's  foot  it  is  only  about  0.5 
millimeter  in  one  second.  In  those  of  the  mesentery  of  a  young  dog  it  has 
been  found  to  be  0.8  millimeter;  in  those  of  the  human  retina,  from  0.6  to 
0.9  millimeter. 

Speed  and  Pressure  of  the  Blood  Compared. —  If  now  we  compare  the 
speed  with  the  pressure  of  the  blood  in  the  arteries,  in  the  capillaries,  and  in 
the  veins,  we  shall  be  struck  by  both  similarities  ami  differences.  In  the 
arteries  both  pressure  and  speed  rhythmically  rise  and  fall  together  \  and  both 
the  mean  pressure  and  the  mean  speed  decline  from  the  heart  to  the  capillaries. 
In  the  capillaries  both  pressure  and  speed  are  pulseless  and  low, — very  low 
compared  with  the  great  arteries.  In  the  veins,  however,  the  pressure  is 
everywhere  lower  than  in  the  capillaries  and  falls  Prom  the  capillaries  to  the 
heart;  the  speed  is  everywhere  higher  than   in   the  capillaries  and    rises  from 

1  M.  L.  Lortet:  Recherches  sur  /"  vitesse  du  coura  </"  tang  danslea  art&res  du  cheval  au  m  a 
d'un  nouvel  hemodromiifiriijili:,  l'.nis.  lsr.7. 

2  J.  Dogiel  :  loc.  eil. 

3  E.  Cyon  und  P.  Steinmann :  "  Die  Geechwindigkeil  iK-s  Blutstroma  in  den  Venen,"  Bulletin 
de  I'Academie  Imperial*  den  Sciences  ,1c  St.  Peiersbmirfj,  1871  ;  also  in  E.  I  !yon  :  QesamnuUe  physio- 
logisehe  Arbeitm,  1888.  S.  110. 

1  K.  Vierordt :  Die  Erscheinungen  und  Oeselze  der  StromgeachwindigkeUen  da  Blutee,  etc.,  1862, 
8.41,111. 


102  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

the  capillaries  to  the  heart.  It  is  apparent,  therefore,  that  there  is  do  direct 
connection  between  the  pressure  and  the  speed  of  the  blood  at  a  given  point, 
inasmuch  a~  they  change  together  along  the  arteries  and  change  inversely 
along  the  veins.  How  varied  the  combinations  may  be  of  pressure  and  speed 
will  be  -ecu  in  studying  the  regulation  of  the  circulation. 

In  the  great  veins,  as  in  the  arteries,  the  speed  is  very  high  compared  with 
the  capillaries.  In  the  capillaries  the  speed  of  the  blood  is  least,  while  in 
the  tubes  which  supply  and  which  drain  them  the  speed  is  great.  The  physi- 
ological value  of  these  facts  is  clear.  It  has  already  been  pointed  out  that  the 
blood  moves  slowly  through  the  short  and  narrow  tubes,  where  its  exchanges 
with  tissue  and  with  air  are  effected,  and  swiftly  through  the  long  tubes  of 
communication.  What  are  the  physical  conditions  which  underlie  these 
physiological  facts '.' 

The  speed  of  the  blood  varies  inversely  as  the  collective  sectional 
area  of  its  path.  If  the  circulation  in  an  animal  continue  uniform  for  a  time 
— during  several  breaths  and  heart-beats — it  is  evident  that  the  forces  con- 
cerned must  be  so  balanced  that,  during  that  time,  equal  quantities  of  blood 
will  have  entered  and  left  the  heart,  the  arteries,  the  capillaries,  and  the  veins, 
respectively.  If  the  arteries,  for  instance,  lose  more  blood  than  the  heart 
transmits  to  them,  this  blood  must  accumulate  in  the  veins  till  the  arteries 
Income  drained  and  the  supply  to  the  capillaries  fails.  The  very  maintenance 
of  a  circulation,  then,  implies  that  equal  quantities  of  blood  must  pass  any 
two  points  of  the  collective  blood-path  in  equal  times,  except  when  a  general 
readjustment  of  the  rate  of  flow  may  lead  to  a  temporary  disturbance  of  it. 
It  will  be  seen  at  once  that  this  principle  is  consistent  with  the  widest  differ- 
ences of  rate  between  individual  arteries  of  the  same  importance,  or  between 
individual  veins  or  capillaries.  If  in  one  artery  "the  flow  be  increased  by  one- 
half,  and  in  another  be  diminished  by  one-half,  the  total  flow  in  the  two 
arteries  collectively   will  be  the  same  as  before. 

If  the  principle  just  stated  be  considered  in  connection  with  the  anatomy 
of  the  blood-path,  the  differences  of  speed  in  the  arterial,  capillary,  and  venous 
systems  will  at  once  be  understood.  The  wider  arteries  and  veins  are  few. 
Dissection  shows  that  when  an  artery  or  vein  divides,  the  calibre,  and,  with 
the  calibre,  the  "sectional  area"  of  the  branches  taken  together,  is  commonly 
larger  than  that  of  the  parent  trunk.  In  general  it  is  a  law  of  the  arterial 
and  venous  anatomy  that  the  collective  sectional  area  of  the  vessels  of  either 
system  increases  from  the  heart  to  the  capillaries.  The  smaller  the  individual 
vessels  are,  th"  wider  is  the  blood-path  which  they  make  up  collectively. 
Widest  of  all  is  the'  blood-path  where  the  individual  vessels  are  smallest — that 
i-.  in  tin'  capillary  system.  The  collective  sectional  area  of  the  capillaries  is 
several  hundred  times  that  of  the  root  of  the  aorta.  The  collective  sectional 
ana  of  the  veins  which  enter  the  right  auricle  is  greater,  perhaps  twice  as 
great,  as  that  of  the  root  of  the  aorta.  The  venous  system,  regarded  as  a 
single  tube,  is  of  much  greater  calibre  than  the  arterial.  It  is  perhaps  better 
to  make  these  general  statements  than  to  compare  the  different  figures  giveu 


CIR  CULA  TIOX.  1 03 

by  different  observers.  The  arterial  and  venous  systems,  treated  as  each  a 
single  tube,  may  be  compared  roughly  to  two  funnels,  cadi  having  its  nar- 
row end  at  the  heart.  The  very  wide  and  very  short  single  tube  of  the  capil- 
lary system  may  be  imagined  to  connect  the  wide  end-  of  the  two  funnels. 
Equal  quantities' of  blood  pass  in  equal  times  any  two  points  of  the  collec- 
tive blood-path  between  the  left  ventricle  and  the  righl  auricle.  Therefore 
where  the  blood-path  is  wide,  these  quantities  must  move  slowly,  and  swiftly 
where  the  blood-path  is  narrow.  It  is  owing,  then,  to  the  rapid  widening  of 
the  arterial  path  that  the  speed  declines,  like  the  pressure,  toward  the  capilla- 
ries. It  is  owing  to  the  huge  relative  calibre  of  the  path  at  the  capillaries 
that  in  them  the  speed  is  by  far  the  least  while  the  same  volume  is  passing 
that  passes  a  point  in  the  narrow  aorta  in  the  same  time  ;  it  is  owing  to  the 
steady  narrowing  of  the  venous  path  toward  the  heart  that  the  venous  blood 
is  constantly  quickening  its  speed  while  its  pressure  is  falling.  As  the  calibre 
of  the  venous  system  is  greater  than  that  of  the  arterial,  the  average  -peed  in 
the  veins  is  probably  less  than  in  the  arteries.  As  the  collective  calibre  of 
the  veins  which  enter  the  right  auricle  is  greater  than  that  of  the  aorta,  the 
blood  probably  moves  into  the  heart  less  swiftly  than  out  of  it;  though  <>i' 
course  equal  quantities  enter  and  leave  it  in  equal  times  provided  those  times 
are  not  mere  fractions  of  a  beat.  In  connection  with  this  it  is  significant 
that  the  entrance  of  blood  into  the  heart  takes  place  during  the  long  auric- 
ular diastole,  while  its  exit  is  limited  to  the  shorter  ventricular  systole. 

Time  Spent  by  the  Blood  in  a  Systemic  Capillary. —  The  width  of  the 
path,  then,  determines  the  slow  movement  of  the  blood  in  the  areas  where  it  is 
fulfilling  its  functions;  the  narrowness  of  the  path,  the  swiftness  of  move- 
ment of  the  blood  in  leaving  and  returning  to  the  heart.  We  have  seen  (p. 
79)  that  a  particle  of  blood  may  make  the  entire  round  of  a  dog's  circulation 
in  from  fifteen  to  eighteen  seconds.  If  we  assume  the  systemic  capillary  flow 
to  be  at  the  rate  of  0.8  millimeter  in  one  second,  the  blood  would  remain  about 
0.6  of  a  second  in  a  systemic  capillary  half  a  millimeter  long.  Slow  as  is  the 
capillary  flow,  it  thus  appears  that  it  is  none  too  slow  to  give  time  for  the  usas 
of  the  blood  to  be  fulfilled. 

F.  The  Flow  of  Blood  through  the  Lungs. 
The  blood  moves  from  the  right  ventricle  to  the  left  auricle  under  the 
same  general  laws  as  from  the  left  ventricle  to  the  right  auricle.  Certain  dif- 
ferences, however,  are  apparent,  and  must  he  noted.  One  difference  is  that 
the  collective  friction  is  less  in  the  pulmonary  than  in  the  systemic  vessels, 
and  that  therefore  the  resistance  to  be  overcome  by  each  contraction  of  the 
right  ventricle  is  less  than  that  opposed  to  the  left  ventricle.  Accordingly  it 
appears  from  dissection  that  the  muscular  wall  of  the  right  ventricle  is  much 
thinner  than  that  of  the  left,  No  accurate  measurements  can  he  made  of  the 
normal  pressure  and  speed  of  the  blood  in  the  arteries,  capillaries,  and  veins 
of  the  lungs,  because  they  can  lie  reached  only  by  opening  the  chest  and 
destroying  the  mechanism  of  respiration,  and   thereby  disturbing   the   normal 


L04  AN   AMERICAN    TEXT-BOOK    OF  PHYSIO  LOO  V. 

conditions  of  the  pulmonary  blood-stream.     In  the  opened  chest  these  cannot 

I otirely  restored  by  artificial   respiration.     The  thinness  of  the  wall  of  the 

pulmonary  artery,  however,  indicates  that  it  has  much  less  pressure  to  support 
than  that  of  the  aorta,  which  fact  also  is  indicated  by  such  roughly  approxi- 
mate  results  as  have  been  obtained   with  the   manometer  after  opening  the 

chest. 

As  the  pulmonary  artery  and  veins  lie  wholly  within  the  chest,  but  outside 
the  lungs,  their  trunks  and  larger  branches  all  tend  to  be  dilated  continuously 
by  i lie  elastic  pull  of  the  lungs — a  pull  which  increases  at  each  inspiration. 
( )n  i  lie  other  hand,  tin1  pulmonary  capillaries  lie  so  close  to  the  surface  of  each 
lung  that  they  are  exposed  to  the  same  pressure,  practically,  as  that  surface, 
and  the  full  weight  of  the  atmosphere  may  act  upon  them.  These  conditions 
all  tend  to  unload  the  capillaries  and  the  pulmonary  veins,  but  to  weaken  the 
unloading  of  the  pulmonary  artery.  The  two  eifects  can  hardly  balance  one 
another,  however.  The  wall  of  the  pulmonary  artery  is  so  much  stiffer  than 
that  of  the  vein,  that  the  actual  results  should  be  favorable  to  the  flow.  The 
elasticity  of  the  lungs  and  the  contractions  of  the  muscles  of  inspiration  thus 
lighten,  probably,  the  work  of  the  right  ventricle  as  well  as  of  the  left.  The 
right  ventricle,  however,  like  the  left,  can  accomplish  its  work  without  assist- 
ance ;  for  the  entire  circulation,  including,  of  course,  the  flow  through  the 
lung-,  continues  after  the  chest  has  been  opened,  if  artificial  respiration  be 
maintained. 

G.  The  Pulse-volume  and  the  Work  done  by  the  Ventricles 

of  the  Heart. 

The  Cardiac  Cycle. — It  is  assumed  that  the  anatomy  of  the  heart  is  known 
to  the  reader. 

The  general  nature  and  effects  of  the  heart's  beat  have  been  sketched 
already.  Each  beat  has  been  seen  to  comprise  a  number  of  phenomena,  which 
occur  in  regular  order,  and  which  recur  in  the  same  order  during  each  of  the 
succeeding  beats.  Each  beat  is  therefore  a  cycle;  and  the  phrase  "  cardiac 
cycle"  has  become  a  technical  expression  for  "  beat,"  as  it  conveys,  in  a  word, 
the  idea  of  a  regular  order  of  events.  As  each  of  the  four  chambers  of  the 
heart  has  its  own  systole  and  diastole,  there  are  eight  events  to  be  studied  in 
connection  with  each  cycle.  The  systoles  of  the  two  auricles,  however,  are 
exactly  simultaneous,  as  are  their  diastoles ;  and  the  same  is  true  of  the  sys- 
toles and  of  the  diastoles  of  the  two  ventricles.  We  may,  therefore,  without 
confusion,  speak  of  the  auricular  systole  and  diastole,  and  of  the  ventric- 
ular systole  and  diastole,  as  of  four  events,  each  involving  the  narrowing  or 
widening  of  two  chambers,  a  right  and  a  left.  The  heart  of  the  mammal 
or  bird  consists  essentially  of  a  pair  of  pumps,  the  ventricles,  each  of  which 
acts  alternately  as  a  powerful  force-pump  and  as  a  very  feeble  suction- 
pump.  To  each  ventricle  is  superadded  a  contractile  appendage,  the  auricle, 
through  which,  and  to  some  extent  by  the  agency  of  which,  blood  enters  the 
ventricle. 


CIRCULATION.  105 

The  Pulse- volume. — The  central  fact  of  the  circulation  of  the  blood  is  the 
injection,  at  intervals,  by  each  ventricle,  against  a  strong  resistance,  of  a  charge 
of  blood  into  its  artery,  which  charge  the  ventricle  has  just  received  out  of  its 
veins  through  its  auricle.  This  quantity  must  be  exactly  the  same  for  the 
two  ventricles  under  normal  conditions,  or  the  circulation  would  soon  come  to 
an  end  by  the  accumulation  of  the  blood  in  either  the  pulmonary  or  the  sys- 
temic vessels.  The  blood  ejected  from  each  vent  ride  during  the  systole 
must  also  be  equal  in  volume  to  the  blood  which  enters  each  set  of  capillaries, 
the  pulmonary  or  systemic,  during  that  systole  and  the  succeeding  diastole  of 
the  ventricles,  provided  the  circulation  be  proceeding  uniformly.  The  quantity 
just  referred  to  is  called  the  "contraction  volume"  or  "pulse-volume"  of  the 
heart.  Were  it  always  the  same,  and  could  we  measure  it,  we  should  possess 
the  key  to  the  quantitative  study  of  the  circulation. 

The  pulse-volume  may  vary  in  the  same  heart  at  different  times,  as  is  easily 
shown  by  opening  the  chest,  causing  the  conditions  of  the  circulation  to  change, 
and  noting  that  under  certain  conditions  the  heart  during  each  beat  varies 
in  size  more  than  before.  This  variation  of  volume  is  easily  possible  because 
the  walls  of  the  heart  are  of  muscle,  soft  and  distensible  when  relaxed.  It  is 
probable  that  at  no  systole  is  the  ventricle  quite  emptied  ;  that  most  of  its 
cavity  may  become  obliterated  by  the  coming  together  of  its  walls,  but  that  a 
space  remains,  just  below  the  valves  and  above  the  papillary  muscles,  which  is 
not  cleared  of  blood.  It  is  also  probable  that  not  only  the  blood  which  is 
ejected  at  the  systole  may  vary  in  amount,  but  also  the  residual  blood  which 
remains  in  the  ventricle  at  the  end  of  the  systole.1  It  is  therefore  clear  that 
it  is  useless  to  attempt  the  measurement  of  the  pulse-volume  by  measuring 
the  fluid  needed  to  fill  the  ventricle,  even  if  the  heart  be  freshly  excised  from 
the  living  body  and  injected  under  the  normal  blood-pressure.  Rough  approx- 
imations to  this  measurement  may,  however,  be  attempted  in  at  least  two 
ways : 

In  the  first  place,  a  modification  of  the  stromuhr  has  been  applied  suc- 
cessfully to  the  aorta  of  the  rabbit,  bet  ween  the  origins  of  the  coronary  arteries 
and  of  the  innominate.  This  operation  requires  thai  the  auricles  be  clamped 
temporarily  so  as  to  stop  the  flow  of  blood  into  the  ventricle.-,  and  to  permit 
the  aorta  in  its  turn  to  be  clamped  and  divided  between  the  clamp  and  the 
ventricle,  without  serious  bleeding.  A.fter  the  circulation  lias  been  re-estab- 
lished, the  volume  of  the  blood  which  passes  through  the  instrument  during 
the  experiment,  divided  by  the  number  of  the  heart-beats  during  the  same 
period,  gives  the  pulse-volume.     The  average  result  obtained,  for  the  rabbit, 

1  F.Hesse:  "Beitriige  zur  Mechanik  der  Herzbewegung,"  Archivfiir  Anatomic  und  Phyaiolo- 
gie  (anatomische  Abtheilung),  L880,  S.  328.  C.  Sandborg  und  W.  Miiller  :  "  Studien  fiber  den 
Mechanismus  des  fferzens,"  Pfluger'a  Archiv  fur  die  gesammle  Physiologic,  L880,  \\ii.  S.  408.  C.S. 
Roy  and  J.  G.  Adami:  "Contributions  to  the  Physiology  and  Pathology  of  the  Mammalian 
Heart,"  Proceedings  <;/'  tic  l,'<>i/<il  Society  •;/'  London,  1891-92,  i.  \>.  435.  .1.  E.  Johansson  und  R. 
Tigerstedt :  " Ueber  die  gegenseitigen  Beziehungen  des  Herzens  und  der  Oefasse  f  "Ueberdie 
Herzthiitigkeit  bei  verschieden  <jrossem  Wiederstand  in  den  Uefassen,"  Skandinavisches  Archiv 
fur  Physiologic,  1891,  ii.  S.  409. 


106  AN    AMERICAN    TE XT-BOOK   OF  PHYSIOLOGY. 

is  a  volume  of  blood  the  weight  of  which  is  0.00027  of  the  weight  of  the 
animal.1 

A  second  way  of  attempting  t<>  ascertain  the  pulse-volume  is  to  measure  the 
swelling  and  the  shrinkage  of  the  heart.  This  is  called  the  "plethysmography" 2 
method.  <  me  application  of  it  is  as  follows  :  The  chest  and  pericardium  of  an 
animal  are  opened,  and  the  heart  is  inserted  into  a  brass  ease  full  of  oil.  The 
opening  through  which  the  great  vessels  pass  is  made  water-tight  by  mechanical 
means  which  do  not  impede  the  movement  of  the  blood  into  and  out  of  the 
heart.  The  top  of  the  brass  case  is  prolonged  into  a  tube,  the  oil  in  which 
rises  as  the  heart  swells  and  falls  as  it  shrinks.  Upon  the  oil  a  light  piston 
move-  up  and  down,  and  records  its  movements  upon  the  kymograph.  The 
instrument  is  called  a  "  eardiometer."  3 

The  average  pulse-volume  of  the  human  ventricle  has  been  very  variously 
estimated  upon  the  basis  of  observations  of  various  kinds  made  upon  mam- 
mals of  various  species.  The  figures  offered  range,  in  round  numbers,  from 
•"><)  to  190  cubic  centimeters.  \{'  we  assume  the  human  pulse-volume  to 
weigh  100  grams,  and  the  blood  of  a  man  who  weighs  69  kilograms  to  weigh 
5.308  kilograms,  or  y1^  of  his  body-weight,  the  pulse-volume  will  be  about  -^ 
of  the  entire  blood,  and  the  entire  blood  will  pass  through  the  heart,  from 
the  veins  to  the  arteries,  in  only  fifty-three  beats — that  is,  in  less  than  one 
minute.  The  speed  with  which  a  man  may  bleed  to  death  if  a  great  artery 
be  severed   is  therefore  not  surprising. 

The  Work  done  by  the  Contracting-  Ventricles. — Uncertain  as  is  this 
important  quantity  of  the  pulse-volume,  the  estimation  of  the  work  done  by  the 
heart  in  maintaining  the  circulation  must  be  based  upon  it,  and  upon  the  force 
with  which  each  ventricle  ejects  the  pulse-volume.  A  small  fraction  of  this 
force  is  expended  in  imparting  a  certain  velocity  to  the  ejected  blood  ;  all  the 
rest  serves  to  overcome  a  uumber  of  opposing  forces.  The  force  exerted  by 
the  muscular  contraction  is  opposed  by  the  weight  of  the  volume  ejected,  and 
by  the  strong  arterial  pressure,  which  resists  the  opening  of  the  semilunar 
valve  and  the  ejection  of  the  pulse-volume.  Moreover,  the  elasticity  of  the 
lung-  tend-  at  all  times  to  dilate  the  ventricles,  with  a  force  which  is  increased 
at  each  recurring  contraction  of  the  muscles  of  inspiration.  Probably  there  is 
also  in  the  wall  of  the  ventricle  itself  a  slight  elasticity  which  must  be  over- 
come by  the  ventricle's  own  contraction  in  orderthat  its  cavity  may  be  effaced, 
The  -trong  arterial  pressure,  with  which  the  reader  is  already  familiar,  is  by 
far  the  greatest  of  these  resisting  forces — in  fact,  is  the  only  one  of  them 
which  is  not  of  small  importance  in  the  present  connection. 

Are  we  obliged  to  measure  the  force  of  the  systole  indirectly  ?  ('an  we  not 
ascertain  it  by  direct  experiment ".'  Manometers  of  various  kinds  have  been 
placed  in  direct  communication  with  the  cavities  of  the  ventricles.     The  fol- 

1  It.   Tisjerstedt:  "  Studien  uber  die    Blutvertheilnng   im    Korper."     Erste  Abhandlung. 

"Bestimmnng  der  von  deni  linken  Herzen  herausgetriebenen  Blutmenge,"  Skandinavisches 
Arilur  fiir  Phygiologie,  1891,  iii-  S.  145. 

n-  From  ~?7/th>Gfi6c,  enlargement.  3  C  S.  Roy  and  J.  G.  Adami,  op.  oil. 


CIRCULATION.  L07 

lowing  method,  among  others,  has  been  employed  :  A  tube  open  at  both  ends 
is  introduced  through  the  external  jugular  vein  of  an  animal  into  the  right 
ventricle,  or,  with  greater  difficulty,  through  the  carotid  artery  into  the  left 
ventricle.  In  neither  case  is  the  valve,  whether  tricuspid  or  aortic,  rendered 
incompetent  during  this  proceeding,  nor  need  the  general  mechanism  of  the 
heart  and  vessels  be  gravely  disturbed.  If  the  outer  end  of  the  tube  be 
connected  with  a  recording  mercurial  manometer,  a  tracing  of  the  pressure 
within  the  right  or  left  ventricle  may  be  written  upon  the  kymograph.  It 
is  found,  however,  that  the  pressure  within  the  heart  varies  so  much  and  so 
rapidly  that  the  inert  mercurial  column  will  not  follow  the  fluctuations,  and 
that  the  attempt  to  learu  the  mean  pressure  by  this  method  fails.  A  valve, 
however,  may  be  intercalated  in  the  tube  between  the  ventricle  and  the  man- 
ometer— a  valve  so  made  as  to  admit  fluid  freely  to  the  manometer,  but  to  let 
none  out.  The  manometer  will  then  record,  and  record  not  too  incorrectly,  the 
maximum  pressure  within  the  right  or  left  ventricle  during  the  experiment;  in 
other  words,  it  will  record  the  greatest  force  exerted  during  that  time  by  the  ven- 
tricle in  order  to  do  its  work.1  In  this  way  the  maximum  pressure  within 
the  left  ventricle  of  the  dog  has  been  found  to  present  such  values  as  170  and 
234  millimeters  of  mercury,  the  corresponding  maximum  pressure  in  the  aorta 
being  158  and  21 2  millimeters  respectively.2  The  maximum  pressures  obtained 
from  simultaneous  observations  upon  the  right  and  left  ventricle  of  a  dog  are 
variously  reported.  It  would  perhaps  be  not  far  wrong  to  say  that  in  this 
animal  the  pressure  in  the  right  ventricle  is  to  that  in  the  left  as  1  to  2.6.3 

The  work  done  by  each  ventricle  during  its  systole  is  found  by  multiplying 
the  weight  of  the  pulse-volume  ejected  into  the  force  put  forth  in  ejecting  it. 
That  force  is  equal  to  the  pressure  under  which  the  pulse  volume  is  expelled. 
If  we  use  as  a  basis  of  calculation  the  pressures  observed  in  the  dog's  heart  with 
the  maximum  manometer,  we  may  assume  as  the  measure  of  a  given  pressure 
within  the  contracting  human  left  ventricle  200  millimeters  of  mercury,  and  for 
the  human  right  ventricle  77  millimeters.  If  for  each  column  of  mercury  there 
be  substituted  the  corresponding  column  of  blood,  the  heights  will  be  2.5fi7 
meters  and  0.988  meter  respectively.  The  force  exerted  by  the  right  or  left 
ventricle  upon  the  pulse-volume  might  therefore  just  equal  that  put  forth  in 
lifting  it  to  a  height  of  0.988  or  2.507  meters.  If  we  assume  100  grams  as 
the  weight  of  a  possible  pulse-volume  ejected  by  a  human  ventricle,  the  work 
done  at  each  systole  of  the  left  ventricle  would  be  1<»<>  2.567  25<i.7  gram- 
meters,  and  at  each  systole  of  the  right  ventricle  100  0.988  98.8  gram- 
meters;  a  grammeter  being  the  work  done  in  raising  one  gram  to  the  height 
of  one  meter.  The  work  of  both  ventricles  together  would  be  256.7  H  98.8 
=  355.5  grammeters.  The  foregoing  estimates  are  offered  not  :is  statements 
of  what  does  occur,  but  as  very  rough  indications  of  whal  may  occur.     Even 

1  F.  Goltz  iind  J.  Gaule:  "  Ueber  die  Druckverhaltnisse  im  [nnera  ties  Herzens,"  Archiv 

J'iir  die  (/esammtr  Phyxiolni/ii',  187N,  xvii.   S.  100. 

2  S.  de  Jager :  "  Ueber  die  Saugknilt  dea  Herzens,"  Pfluger'a  Archiv  fur  du  gesammte  Physic 
ologie,  1883,  S.  504,  505.  <  ;"li/.  '"><'  (  *aule,  op.  tit.,  S.  106. 


108  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

1 1 1 1 1 — ,  however,  they  are  of  moment.  When  we  think  of  the  vast  number  of 
beats  executed  by  the  heart  every  day,  the  great  amount  of  energy  rendered 
manifest  in  maintaining  the  circulation  becomes  apparent,  and  our  interest  is 
heightened  in  the  fact  that  all  of  this  large  sum  of  energy  is  liberated  in  the 
muscular  tissue  of  the  heart  itself.  Thus,  too,  the  physiological  significance 
nt'  the  diastole  is  accentuated  as  a  time  of  rest  for  the  cardiac  muscle,  as  well 
as  a  necessary  pause  for  the  admission  of  blood  into  the  ventricle.  To  disre- 
gard minor  considerations,  the  work  dune  at  a  systole  will  evidently  depend 
upon  the  amount  of  the  pulse-volume,  of  the  arterial  pressure  overcome,  and 
of  the  velocity  imparted  to  the  ejected  blood.  All  these  are  variable.  The 
work  of  the  ventricles  therefore  is  eminently  variable. 

The  Heart's  Contraction  as  a  Source  of  Heat. — In  dealing  with  the 
movement  of  the  blood  in  the  vessels  we  have  seen  that  the  energy  of  visible 
motion  liberated  by  the  cardiac  contractions  is  progressively  changed  into  heat 
by  the  friction  encountered  by  the  blood  ;  and  that  this  change  is  nearly  com- 
plete by  the  time  the  blood  has  returned  to  the  heart,  the  kinetic  energy  of 
each  systole  sufficing  to  drive  the  blood  from  the  heart  back  to  the  heart  again, 
but  probably  not  being  much  more  than  is  required  for  this  purpose.  Practi- 
cally, therefore,  all  the  energy  of  the  heart's  contraction  becomes  heat  within 
the  body  itself,  and  leaves  the  body  under  this  form.  As  the  heart  liberates 
during  every  day  an  amount  of  energy  which  is  always  large  but  very  variable, 
it-  contractions  evidently  make  no  mean  contribution  to  the  heat  produced  in 
the  body  and  parted  with  at  its  surface. 

H.  The  Mechanism  of  the  Valves  of  the  Heart. 

Use  and  Importance  of  the  Valves. — The  discussion  just  concluded 
show-  the  work  of  the  heart  to  be  the  forcible  pumping  of  a  variable  pulse- 
volume  out  of  veins  where  the  pressure  is  low  into  arteries  where  the  pressure 
is  high.  It  is  owing  to  the  valves  that  this  is  possible,  and  so  dependent  is 
the  normal  movement  of  the  blood  upon  the  valves  at  the  four  ventricular 
apertures  that  the  crippling  of  a  single  valve  by  disease  may  suffice  to  destroy 
life  after  a  longer  or  -holier  period  of  impaired  circulation. 

The  Auriculo-ventricular  Valves. — The  working  of  the  auriculo-ven- 
tricular  valves  (see  Fig.  18)  is  not  hard  to  grasp.  When  the  pressure  within 
the  ventricle  in  its  diastole  is  low,  the  curtains  hang  five  in  the  ventricle, 
although  probably  never  in  close  contact  with  its  wall.  As  the  blood  pours 
into  the  ventricle,  the  pressure  within  it  rises,  currents  How  into  the  space  be- 
tween the  wall  and  the  valve,  and  probably  bring  near  together  the  edges  of 
the  curtains  and  also  their  surfaces  for  some  distance  from  the  edge.-.  Thus, 
upon  tin'  cessation  of  the  auricular  systole,  the  supervening  of  a  superior  pres- 
sure  within  the  ventricle  probably  applies  the  already  approximated  edges 
and  surfaces  of  the  curtains  to  one  another  so  promptly  that  the  commencing 
contraction  of  the  ventricle  is  not  attended  by  regurgitation  into  the  auricle. 
The  principle  of  closure  is  the  same  for  the  tricuspid  valve  as  for  the  mi- 
tral.     A-   the   force-  are   exactly  equal  and   opposite  which    press  together  the 


CIBCULA  TION. 


109 


opposed  parts  of  the  surfaces  of  the  curtains,  those  parts  undergo  no  strain, 
aud  hence  are  enabled  to  be  exquisitely  delicate  and  flexible  and  therefore 
easily  fitted  to  oue  another.  On  the  other  hand,  the  parts  of  the  valve  which 
intervene  between  the  surfaces  of  contact  aud  the  auriculo-ventricular  ring  are 
tough  and  much  thicker,  as  they  have  to  bear  the  brunt  of  the  pressure  within 
the  contracting  ventricle.  As  the  systole  of  the  ventricle  increases,  the  auric- 
ulo-ventricular ring  probably  becomes  smaller,  aud  the  curtains  of  the  valve 
probably  become  somewhat  fluted  from  base  to  apex,  so  that  their  line  of  & in- 
tact is  a  zig-zag.  At  the  same  time  their  surfaces  of  contact  may  increase  in 
extent. 

Tendinous  Cords  and  their  Uses. — The  structure  so  far  described  is 
wonderfully  effective  because  it  is  combined  with  au  arrangement  to  prevent  a 
reversal  of  the  valve  into  the  auricle,  which  otherwise  would  occur  at  ouce. 
This  arrangement  cousists  in  the  disposition  of  the  tendinous  cords,  which  act 


Fig.  is.— 'rile  left  ventricle  and  aorta  Laid  open,  t>>  show  the  mitral  ami  aortic  semilunar  valves  i  Efenle). 


as  guy-ropes  stretched  between  the  muscular  wall  of  the  ventricle  aud  the 
valve,  whether  mitral  or  tricuspid.  These  cords  are  tough  and  inelastic,  and, 
like  the  valve,  are  coated  with  the  slippery  lining  of  the  heart.  They  are 
stout  where  they  spring  from  the  muscle,  but  divide  and  subdivide  into 
branches,  strong  but   sometimes  very  fine,  which  proceed   fan-wise  Prom  their 


IK)  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

stem  to  their  insertions  (see  Fig.  18).  These  insertions  are  both  into  the  free 
margin  of  the  valve  and  into  the  whole  extent  of  that  surface  of*  it  which 
looks  toward  the  wall  of  the  ventricle,  quite  up  to  the  ring.  By  means  of  this 
arrangement  of  the  cords  cadi  curtain  is  held  taut  from  base  to  apex  through- 
out the  systole  of  the  ventricles,  the  opposed  surfaces  being  kept  in  apposition, 
and  the  parts  of  the  curtains  between  these  surfaces  and  the  ring  being  kept 
from  bellying  unduly  toward  the  auricle.  Each  curtain  is  held  sufficiently 
taut  from  side  to  side  as  well,  because  the  tendinous  cords  inserted  into  one 
lateral  half  of  the  curtain  spring  from  a  widely  different  part  of  the  wall  of 
the  heart  from  those  of  the  other  lateral  half  of  it  (see  Fig.  18).  At  all  times, 
therefore,  even  when  the  walls  of  the  ventricle  are  most  closely  approximated 
during  systole,  the  cords  may  pull  in  slightly  divergent  directions  upon  the 
two  lateral  halves  of  each  curtain.  This  arrangement  of  the  cords  may  also 
cause  them,  when  taut,  to  pull  in  slightly  convergent  directions  upon  the 
contiguous  lateral  halves  of  two  neighboring  curtains  and  thus  to  favor  the 
pressing  of  them  together  (see  Fig.  18). 

Papillary  Muscles  and  their  Uses. — In  the  left  ventricle  the  tendinous 
cords  arise  in  two  groups,  like  bouquets,  from  two  teat-like  muscular  projec- 
tion- which  spring  from  opposite  points  of  the  wall  of  the  heart,  and  which 
are  called  the  "papillary  muscles  "  (see  Fig.  18).  One  of  these  gives  origin 
to  the  cords  for  the  right  half  of  the  anterior  and  for  the  right  half  of  the 
posterior  curtain  ;  the  other  papillary  muscle  gives  rise  to  the  cords  for  the 
left  halves  of  the  two  curtains.  Each  papillary  muscle  is  commonly  more  or 
less  subdivided  (see  Fig.  18).  The  same  principles  are  carried  out,  but  less 
regularlv,  for  the  origins  of  the  tendinous  cords  of  the  more  complex  tricuspid 
valve.  Various  opinions  have  been  held  as  to  the  use  of  the  papillary  muscles. 
It  seems  probable  that  during  the  change  of  size  and  form  wrought  in  the 
ventricle  by  its  systole,  the  origins  of  the  tendinous  cords  and  the  auriculo- 
ventricular  ring  tend  to  be  approximated  and  the  cords  to  be  slackened  in 
consequence.  Perhaps  this  is  checked  by  a  compensatory  shortening  of  the 
papillary  muscles,  due  to  their  sharing  in  the  systolic  contraction  of  the  mus- 
cular ma>s  of  which  they  form  a  part.  Observations  have  been  made  which 
have  been  interpreted  to  mean  that  the  papillary  muscles  begin  their  con- 
traction slightly  later  and  end  it  slightly  earlier  than  the  mass  of  the  ven- 
tricle.1 

Semilunar  Valves. — The  anatomy  and  the  working  of  the  semilunar 
valve-  are  the  same  in  the  aorta  as  in  the  pulmonary  artery,  and  one  account 
will  answer  for  both  valves.  Each  valve  is  composed  of  three  entirely  sepa- 
rate segments,  set  end  to  end  within  and  around  the  artery  just  at  its  origin 
from  the  ventricle.  The  attachment-  of  the  segment-  occupy  the  entire  cir- 
cumference of  the  vessel  (Fig.  18).  Like  the  tricuspid  and  mitral  valves, 
each  semilunar  segment  i-  composed  of  a  sheet  of  tissue  which  is  tough,  thin, 
supple,  and  slippery  ;  but  the  semilunar  valves  differ  from  the  tricuspid  and 
3.  Roy  and  .1.  <i.  Adami:     "Heart-beat  and  Pulse-wave,"   The  Practitioner,  1890,  i. 


CIRCULATION. 


Ill 


mitral,  uot  only  in  the  complete  distinctness  of  their  segments,  but  also  in 
their  mechanism.  The  tendinous  cords  are  wholly  lacking,  and  each  segment 
depends  upon  its  direct  connection  with  the  arterial  wall  to  prevent  reversal 
into  the  ventricle  during  the  diastole  of  the  latter.  If  the  artery  be  carefully 
laid  open  by  cutting  exactly  between  two  of  the  segments,  each  of  the  three  is 
seen  to  have  the  form  of  a  pocket  with  its  opening  turned  away  from  the  heart 
(see  Fig.  18).  Behind  each  segment,  the  artery  is  dilated  into  one  of  the  hol- 
lows or  "sinuses"  of  Valsalva.1  As  the  valve  lies  immediately  above  the 
base  of  the  ventricle  the  segments  rest  upon  the  top  of  the  thick  muscular 
wall  of  the  latter,  which  affords  them  a  powerful  support  (see  Fig.  19). 
Each  segment  is  attached  by  the  whole  length  of  its  longer  edge  to  the  artery, 
while  the  free  margin  is  formed  by  the  shorter  edge.  It  is  this  arrangement 
which  renders  reversal  of  a  segment  impossible  (see  Fig.  18). 


Fig.  19.— Diagram  to  illustrate  the  mechanism  of 
the  semilunar  valve. 


Fig.  20.— Diagram  to  illustrate  the  mechanism  of 
the  semilunar  valve  and  corpora  Arantii. 


While  the  blood  is  streaming  from  the  ventricle  into  the  artery,  the  three 
segments  are  pressed  away  by  the  stream  from  the  centre  of  the  vessel,  but 
never  nearly  so  far  as  to  touch  its  wall.  At  all  time-,  therefore,  a  pouch  ex- 
ists behind  each  segment,  which  pouch  freely  communicates  with  the  general 
cavity  of  the  artery.  As  the  ventricular  systole  nears  its  end,  the  ventricular 
cavity  doubtless  becomes  narrowed  just  below  the  root  of  the  artery,  and  with 
it  the  arterial  aperture  itself,  while  currents  enter  the  sinuses  of  Valsalva. 
Thus  for  a  double  reason  the  three  segments  of  the  valve  are  approximated, 
and  probably  the  last  blood  pressed  out  of  the  ventricle  issues  through  a  nar- 
row chink  between  them.  The  instant  that  the  pressure  in  the  ventricle  falls 
below  the  arterial  pressure,  the  three  segments  must  be  brought  together  by 
the  superior  pressure  within  the  artery,  and  tightly  closed  by  it >  forcible  recoil, 
without  regurgitation  having  occurred  in  the  process  (see  Figs.  19,  20). "' 

Lunulse  and  their  Uses. — Each  segment  of  a  semilunar  valve,  when 
closed,  is  in  firm  contact  with  its  fellows  not  only  at  it-  Ih'r  margin  but  also 
over  a  considerable  surface,  marked   in  the  anatomy  of  the  segment   by  the 

two  "lunula?"   or   little  crescents,  each    of  which    occupies    the   surface   of  the 
segment  from  one  of  its  ends  to  the  middle  of  its  {'n^'  margin,  the  shorter  a\<j;v 

1  Named  from  the  Italian  physician  and  anatomist  Valsalva  el'  Bologna,  born  in  1666. 

2  L.  Krehl:  "Beitragezur  Kenntniss  der  Fiillung  und  Entleerung  dea  Herzens,"  Abhand- 
lungen  der  math.-physischen  Clause  der  k.  sdchsiachen  Qesellschqft  de>  II  .  L891,  Bd.  xvii. 
No.  5,  S.  360. 


112  AN   AMERICAN    TEXT-HOOK    OF   PHYSIOLOGY. 

of  the  lunula  being  one-half  of  the  free  margin  of  the  segment  (see  Fig.  18). 
Over  the  surface  of  each  lunula  each  segment  is  in  contact  with  a  different 
one  of  ils  two  fellows  (see  Fig.  20).  The  firmness  of  closure  thus  secured  is 
shown  by  Figure  li»,  which  represents  a  longitudinal  section  of  the  artery, 
passing  through  two  of  the  closed  segments.  The  forces  which  press  together 
the  opposed  surfaces  are  equal  and  opposite,  and  the  parts  of  the  segments 
which  correspond  to  these  surfaces  undergo  do  strain.  The  Lunula?,  therefore, 
like  the  mutually  opposed  portions  of  the  mitral  or  tricuspid  valve,  are  very 
delicate  and  flexible,  while  the  rest  of  each  semilunar  segment  is  strongly 
made,  to  resist  of  itself  the  arterial   pressure. 

Corpora  Arantii  and  their  Uses. — At  the  centre  of  the  free  margin  of 
each  semilunar  segment,  just  between  the  ends  of  the  two  lunula?,  there  is  a 
small  thickening,  more  pronounced  in  the  aorta  than  in  the  pulmonary  artery, 
called  the  "  body  of  Aranzi " *  (corpus  Arantii).  This  thickening  both  rises 
above  the  edge  and  projects  from  the  surface  between  the  lunula?.  When  the 
valve  is  closed,  the  three  corpora  Arantii  come  together  and  exactly  fill  a  small 
triangular  chink,  which  otherwise  might  be  left  open  just  in  the  centre  of  the 
cross  section  of  the  artery  (see  Figs.  18,  20). 

The  foregoing  shows  that  the  mechanism  of  the  semilunar  valves  is  no  less 
effective,  though  far  simpler,  than  that  of  the  mitral  and  tricuspid.  That  the 
latter  two  should  be  more  complex  is  natural  ;  for  each  of  them  must  give 
free  entrance  to  and  prevent  regurgitation  from  a  chamber  which  nearly 
empties  itself,  and  hence  undergoes  a  very  great  relative  change  of  volume  ; 
while  the  arterial  system  is  at  all  times  distended  and  undergoes  a  change  of 
capacity  which  is  relatively  small  while  receiving  a  pulse-volume  and  trans- 
mitting it  to  the  capillaries. 

I.  The  Changes  in  Form  and  Position  of  the  Beating  Heart,  and 

the  Cardiac  Impulse. 

General  Changes  in  the  Heart  and  Arteries. — During  the  brief  systole 
of  the  auricles  these  diminish  in  size  while  the  swelling  of  the  ventricles  is 
completed.  During  the  more  protracted  systole  of  the  ventricles,  which  imme- 
diately follows,  these  diminish  in  size  while  the  auricles  are  swelling  and  the 
injected  arteries  expand  and  lengthen.  During  the  greater  part  of  the  suc- 
ceeding diastole  of  the  ventricles  both  these  and  the  auricles  are  swelling,  and 
all  the  muscular  fibres  of  the  heart  are  flaccid,  up  to  the  moment  when  a  new 
auricular  systole  completes  the  diastolic  distention  of  the  ventricles,  as  above 
stated.  During  the  ventricular  diastole,  as  the  great  arteries  recoil  they 
shrink  and  shorten.  The  changes  of  size  in  the  beating  heart  depend  entirely 
upon  the  changes  in  the  volume  of  blood  contained  in  it,  and  not  upon  changes 
in  the  volume  of  the  muscular  walls.  The  muscular  fibres  of  the  heart  agree 
with  those  found  elsewhere  in  not  changing  their  volume  appreciably  during 
contraction,  but  their  form  only.      The  cardiac  cycle  thus  runs  its  course  with 

1  Named  from  Julius  Ca?sar  Aranzi  of  Bologna,  an  Italian  physician  and  anatomist,  bom 
in  1530. 


Clli<:rLATIOX.  113 

regularly  recurring  changes  of  size  in  the  auricles,  the  ventricles,  and  the 
arteries.  These  changes  of  size  are  accompanied  by  corresponding  changes 
in  the  form  and  position  of  the  heart,  which  are  both  interesting  in  them- 
selves and  important  in  relation  to  the  diagnosis  of  disease.  The  basis 
of  their  study  consists  in  opening  the  chest  and  pericardium  of  an  animal, 
and  seeing,  touching,  and  otherwise  investigating  the  beating  heart.  The 
changes  in  the  beating  heart,  moreover,  underlie  the  production  of  the 
so-called  cardiac  impulse,  or  apex-beat,  which  is  of  interest  in  physical 
diagnosis. 

Observation  of  the  Heart  and  Vessels  in  the  Open  Chest. — The  beat- 
ing heart  may  be  exposed  for  observation  in  a  mammal  by  laying  it  upon  its 
back,  performing  tracheotomy,  and  completely  dividing  the  sternum  in  the 
median  line,  beginning  at  the  ensiform  cartilage.  Artificial  respiration  is  next 
established,  a  tube  having  been  tied  into  the  trachea  before  the  chest  was 
opened.  The  two  sides  of  the  chest  are  now  drawn  asunder  and  the  pericar- 
dium is  laid  open  to  expose  the  heart. 

If,  in  any  mammal,  the  ventricles  be  lightly  taken  between  the  thumb  and 
forefinger,  the  moment  of  their  systole  is  revealed  by  the  sudden  hardening  of 
the  heart  produced  by  it,  as  the  muscular  fibres  contract  and  press  with  force 
upon  the  liquid  within.  On  the  other  hand,  the  ventricular  diastole  is  marked 
by  such  flaccidity  of  the  muscular  fibres  that  very  light  pressure  indents  the 
surface,  and  causes  the  finger  to  sink  into  it,  in  spite  of  care  being  taken  to 
prevent  this.  Commonly,  therefore,  at  the  systole  the  thumb  and  finger  are 
palpably  and  visibly  forced  apart,  no  matter  where  applied,  in  spite  of  the  fact 
that  the  volume  of  the  ventricles  is  diminishing.  This  sinking  of  the  finger 
or  of  an  instrument  into  the  relaxed  wall  of  the  heart  has  given  rise  to  many 
errors  of  observation  regarding  changes  during  the  beat.  The  time  when  tin- 
ventricles  are  hardened  beneath  the  finger  coincides  with  the  up-stroke  of  the 
arterial  pulse  near  the  heart,  and,  as  shown  by  Harvey,1  with  the  time  when 
an  intermittent  jet  of  blood  springs  from  a  wound  of  either  ventricle.  The 
hardening  is  proven  thus  to  mark  the  systole  of  the  ventricles.  Those  changes 
of  size,  form,  and  position  of  the  exposed  heart  which  accompany  the  harden- 
ing of  the  ventricles  beneath  the  finger  are  therefore  the  changes  of  the  ven- 
tricular systole;  and  the  converse  changes  are  those  of  the  ventricular  diastole. 
To  interpret  all  the  changes  correctly  by  the  eye  alone,  without  the  aid  of  tin- 
finger  or  of  the  jet  of  blood,  is  a  tusk  of  surpassing  difficulty  in  a  rapidly  beat- 
ing heart,  as  was  eloquently  set  forth  by  Harvey.2 

Changes  of  Size  and  Form  in  the  Beating  Ventricles. — In  a  mam- 
mal, lying  upon  its  hack,  with  the  heart  exposed,  the  ventricles  evidently 
become  smaller  during  their  systole.  Their  girth  is  everywhere  diminished 
and  their  length  also,  the  latter  mneh  less  than  the  former  j  indeed  the  dimi- 
nution in  length   is  a  disputed  point.     Not  merely  a   change  of  size,   bul   a 

1  Exercitatio  Anatomiea  de  Motti  Cordis  et  Sanguinis  in  Animalibus,  1628,  p.  23;  Willi-'  trans- 
lation, Bowie's  edition,  1889,  p.  23. 

2  Op.  tit.,  1628,  p.  20;  Willis'  translation,  Bowie's  edition,  p.  20. 

Vol.  I.— 8 


114  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

change  of  form  is  thus  produced  ;  the  heart  becomes  a  smaller  and  shorter,  but 
a  more  pointed  cone.  The  narrowing  from  side  to  side  is  very  conspicuous.  Jn 
the  opened  chesi  of  a  mammal  lying  on  its  hack  this  narrowing  is  accompanied 
by  a  change  which  probably  does  not  occur  in  the  unopened  chest,  viz.,  by  some 
increase  in  the  diameter  of  the  heart  from  breasl  to  hack,  so  that  the  surface  of 
the  ventricles  toward  the  observer  becomes  more  convex  (see  p.  116).  Thus 
the  base  of  the  ventricles,  which  tended  to  he  roughly  elliptical  during  their 
relaxation,  tends  to  become  circular  duringtheir  contraction  ;  and  the  diameter 
of  the  circle  is  greater  than  the  shortest  diameter  of  the  ellipse,  which  latter 
diameter  extends  from  breast  to  back.  At  the  same  time,  the  area  of  the  base 
when  circular  and  contracted  is  much  less  than  when  elliptical  and  relaxed.1 
Naturally,  none  of  these  comparisons  to  mathematical  figures  makes  any  pre- 
tence to  exactness.  At  the  same  time  that  the  contracting  heart  undergoes 
these  changes,  the  direction  of  its  long  axis  becomes  altered.  In  animals  in 
which  the  heart  is  oblique  within  the  chest,  the  line  from  the  centre  of  the 
base  to  the  apex,  that  is,  the  long  axis,  while  it  points  in  general  from  head 
to  tail,  points  also  toward  the  breast  and  to  the  left.  In  an  animal  lying  on 
its  back,  the  ventricles  when  relaxed  in  diastole  tend  to  form  an  oblique  cone, 
the  apex  having  subsided  obliquely  to  the  left  and  toward  the  tail.  As  the 
ventricles  harden  in  their  systole,  they  tend  to  change  from  an  oblique  cone  to 
a  right  cone  ;  the  long  axis  tends  to  lie  more  nearly  at  right  angles  to  the  base ; 
and  consequently  the  apex,  unfettered  by  pericardium  or  chest-wall,  makes  a 
slight  sweep  obliquely  toward  the  head  and  to  the  right,  and  thus  rises  up 
bodily  for  a  little  way  toward  the  observer.  This  movement  was  graphically 
called  by  Harvey  the  erection  of  the  heart.2  It  is  accompanied  by  a  slight 
twisting  of  the  ventricles  about  their  long  axis,  in  such  fashion  that  the  left 
ventricle  turns  a  little  toward  the  breast,  the  right  ventricle  toward  the 
back. 

Changes  of  Position  in  the  Beating-  Ventricles. — The  changes  in  form 
imply  changes  in  position.  The  oblique  movement  of  the  long  axis  implies 
that  in  systole  the  mass  of  the  ventricles  sweeps  over  a  little  toward  the 
median  line  and  also  a  little  toward  the  head.  The  shortening  of  the  long 
axis  implies  that  either  the  apex  recedes  from  the  breast,  or  the  base  of  the 
ventricles  recedes  from  the  back,  or  both.  Of  these  last  three  possible  cases, 
the  second  is  the  one  that  occurs.  The  oblique  movement  of  the  apex  is 
accompanied  by  no  recession  of  it;  but  the  auriculo-ventricular  furrow  and 
the  roots  of  the  aorta  and  pulmonary  artery  move  away  from  the  spinal 
column  :i~  the  injected  arteries  lengthen  and  expand,  and,  as  the  auricles  swell, 

during  the  c traction  of  the  ventricles.     During  their  diastole  the  ventricles 

are  soft  ;  they  swell  ;  and  changes  of  form  and  position  occur  which  are 
simply  converse  to  those  of  the  systole  and  have  been  indicated  already  in 
dealing  with  the  latter. 

1  <  .  Ludwig:     "  TJVber  den    Ban  nnd  die  Bewegnngen    der  Herzventrikel,"  Zcitschri/t  fur 

L849,  vii.  8.  189. 

2  Op.  rit.,  162*.  p.  22.     Translation,  L889,  p.  22. 


CIRCULATIOy.  115 

Changes  in  the  Beating-  Auricles. — Except  in  small  animals,  the  walls 
of  both  the  ventricles  are  so  thick  that  the  color  of  the  two  is  the  same  and 
is  unchanging,  namely,  that  of  their  muscular  mass ;  but  the  walls  of  the 
auricles  are  so  thin  that  their  color  is  aiFected  by  that  of  the  blood  within,  so 
that  the  right  auricle  looks  bluish  and  dark  and  the  left  auricle  red  and 
bright.  During  the  brief  systole  of  the  auricles  they  are  seen  to  become 
smaller  and  paler  as  blood  is  expelled  from  them,  while  their  serrated  edges 
and  auricular  appendages  shrink  rapidly  away  from  the  observer.  The 
changes  of  the  auricular  systole  are  seen  to  precede  immediately  the  changes 
of  the  systole  of  the  ventricles  and  to  succeed  the  repose  of  the  whole  heart. 
During  the  relatively  long  diastole  of  the  auricles  these  are  seen  to  swell, 
whether  the  ventricles  are  shrinking  in  systole  or  are  swelling  during  the 
first  and  greater  part  of  their  diastole. 

Changes  in  the  Great  Veins. — In  the  venae  cava?  and  pulmonary  veins  a 
pulse  is  visible,  more  plainly  in  the  former  than  in  the  latter,  which  pulse  has 
the  same  rhythm  as  that  of  the  heart's  beat.  The  causes  of  this  pulse  are 
complex.  It  depends  in  part  upon  the  rhythmic  contraction  of  muscular 
fibres  in  the  walls  of  the  veins  near  the  auricles,  which  must  heighten  the 
flow  into  the  latter,  and  which  contraction  the  auricular  systole  immediately 
follows.1  This  venous  pulse  will  be  mentioned  again  in  discussing  the  details 
of  the  events  of  the  cycle  (see  p.  138). 

Changes  in  the  Great  Arteries. — It  is  interesting  to  note  that  even  in 
so  large  an  animal  as  the  calf  the  pulse  of  the  aorta  or  of  the  pulmonary 
artery  can  hardly  be  appreciated  by  the  eye,  so  far  as  the  increase  in  girth  of 
either  vessel  is  concerned.  The  expansion  of  the  artery  affects  equally  all 
points  in  its  circumference,  and  being  thus  distributed,  is  so  slight  in  propor- 
tion to  the  girth  of  the  vessel  that  the  profile  of  the  latter  scarcely  seems  to 
change  its  place.  The  lengthening  of  the  expanding  artery  can  be  more 
readily  seen. 

Effects  of  Opening  the  Chest. — Such  are  the  changes  observed  in  the 
heart  and  vessels  when  exposed  in  the  opened  chest  of  a  mammal  lying  on 
its  back.  The  question  at  once  arises,  Can  these  changes  be  accepted  as  iden- 
tical with  those  which  occur  in  the  unopened  chest  of  a  quadruped  standing 
upon  its  feet,  or  of  a  man  standing  erect?  It  will  be  most  profitable  to  deal 
at  once  with  the  case  of  the  human  subject.  What  are  the  possible,  indeed 
probable,  differences  between  the  changes  in  the  heart  in  the  unopened  upright 
chest  and  in  the  same  when  opened  and  supine  '.' 

When  air  is  freely  admitted  to  both  pleural  sacs,  all  those  complex  effects 
upon  the  circulation  are  at  once  abolished  which  we  have  seen  to  be  caused 
by  the  elasticity  of  the  lungs  and  the  movements  of  respiration.  The  arti- 
ficial respiration  will  have  an  effect  upon  the  pulmonary  transit  of  the  blood 
and  so  upon  the  circulation  ;  but  the  details  of  this  effeel  are  nol  the  same  as 
those  of  natural  respiration,  and,  for  our  present  purpose,  may  lie  disregarded. 

1  T.  Lauder  Brunton  and  1'".  Fayrer:  "Note  on  [ndependent   Pulsation  of  the  Pulmonary 

Veins  and  Vena  Cava,"  Proceedings  of  tin-  Royal  Sociiti/,  1876,  vol.  \xv.  p.  174. 


111!  AN   AMERICAN    TEXT- HOOK    OF    PHYSIOLOGY. 

"What  has  been  abolished  is  the  continual  suction,  rhythmically  increased  in 
inspiration,  exerted  by  the  lungs  upon  the  heart  and  all  the  vessels  within  the 
chest,  which  suction  at  all  times  favors  the  expansion  and  resists  the  con- 
traction of  the  cavities  of  the  heart  and  of  the  vessels.  On  the  opening  of 
both  pleural  sacs  the  heart  and  vessels  are  exposed  to  the  undiminished  and 
unvarying  pressure  of  the  atmosphere.  Moreover,  the  heart  has  ceased  to  be 
packed,  as  it  were,  between  the  pleurae  and  lungs  to  right  and  left,  the  spine, 
the  front  of  the  chest-wall,  and  the  diaphragm.  From  these  considerations  it 
follows  that  the  heart  must  be  freer  to  change  its  form  and  position  in  the 
opened  than  in  the  unopened  chest;  and  that  these  changes  must  be  more 
modified  by  simple  gravity  in  the  former  case  than  in  the  latter.  Even  in 
the  open  chest  we  have  studied  these  changes  only  in  an  animal  lying  on  its 
back.  But  if  we  turn  the  creature  to  either  side,  or  place  it  upright  in  imi- 
tation of  the  natural  human  posture,  the  ventricles  of  the  exposed  heart  in 
any  case  tend  to  assume,  in  systole,  the  same  form,  which  has  been  com- 
pared roughly  to  a  right  cone  with  a  circular  base.  This  is  the  form  proper 
to  the  hardened  structure  of  branching  and  connected  fibres  of  which  the 
contracting  ventricles  consist.  But  if  the  exposed  ventricles  be  noted  in  dias- 
tole, it  will  appear  that  their  form  depends  very  largely  upon  the  effects  of 
gravity  upon  the  exceedingly  soft  and  yielding  mass  formed  by  their  relaxed 
fibres.  We  have  seen  them,  in  diastole,  to  flatten  from  breast  to  back,  to 
spread  out  from  side  to  side,  to  gravitate  toward  the  tail  and  to  the  left.  If 
the  animal  is  laid  on  its  side,  they  flatten  from  side  to  side,  they  spread 
out  from  breast  to  back,  and  gravitate  to  the  right  or  left,  as  the  case 
may   be.1 

Probable  Changes  in  the  Heart's  Form  and  Position  in  the  Unopened 
Chest. — It  is  fair  to  conjecture  that  the  increase  of  the  relaxed  ventricles  in 
girth  and  in  length  which  is  seen  in  the  open  chest  would  not  be  greatly  differ- 
ent in  the  closed  chest  of  a  man  in  the  upright  posture.  But  it  is  probable 
that  the  flattening  of  the  exposed  heart  from  breast  to  back,  which  is  seen  in 
diastole,  would  not  occur  if  the  chest  were  closed.  It  is  precisely  in  this  direc- 
tion that  the  flaccid  heart  exposed  in  the  supine  chest  Mould  be  flattened  un- 
duly by  its  own  weight,  when  deprived  of  many  of  its  anatomical  supports 
and  of  the  dilating  influence  of  the  lungs.  The  flattening  from  breast  to  back 
must  cause  an  exaggerated  spreading  out  from  side  to  side  and  hence  an  unduly 
elliptical  form  of  the  base,  inasmuch  as,  at  the  same  time,  the  girth  of  the  ven- 
tricles is  increasing  as  they  enlarge  in  their  diastole.  Conversely,  it  is  prob- 
able, both  a  'priori  and  from  experimental  evidence,  that  in  the  chest,  when 
closed  and  upright,  the  diminution  in  size  of  the  contracting  ventricles  pro- 
ceeds more  symmetrically;  thai  their  girth  everywhere  diminishes  through  a 
diminution  of  the  diameter  from  breast  to  back  as  well  as  of  that  from  side  to 

1  J.  B.  Haycraft:  "The  Movements  of  the  Heart  within  the  (lust  cavity,  and  the  <  anlio- 
gram,"  The  Journal  of  Physiology,  vol.  xii.,  Nos.  5  and  G,  December,  1891,  p.  44S ;  J.  B.  Hay- 
craft  and  I).  K.  Paterson  :  "The  Changes  in  Shape  and  in  Position  of  the  Heart  during  the 
Cardiac  Cycle,"  The  Journal  of  Physiology,  vol.  xix.,  Nos.  5  and  6,  May,  1896,  p.  496. 


CIRCULATION.  117 

side,  and  not  through  an  exaggerated  lessening  of  the  latter  and  an  actual 
increase  of  the  former.  In  this  case,  too,  the  base  would  tend  to  become 
more  circular  during  the  systole  by  means  of  a  less  marked  change  from  the 
diastolic  form.1 

It  has  been  said  that  in  systole  the  ventricles  are  somewhat  shortened 
in  the  exposed  heart,  and  probably  also  in  the  unopened  human  chest.  In 
the  open  chest  the  apex  does  not  recede  at  all  in  virtue  of  this  shorten- 
ing ;  on  the  contrary,  the  base  of  the  ventricles  is  seen  to  move  toward 
the  apex,  and  away,  therefore,  from  the  spine.  Experiment  has  proven  that 
the  foregoing  is  true  also  of  the  unopened  chest.2  It  has  been  noted  already 
that  this  movement  of  the  base,  which  in  the  upright  chest  would  be  a  descent, 
is  accompanied  by  a  lengthening  of  the  aorta  aud  pulmonary  artery  as  their 
distention  takes  place.  Very  probably  it  is  the  thrust  of  the  lengthened  arte- 
ries which  largely  causes  the  descent  of  the  base  of  the  contracting  ventricles, 
which  descent  compensates  for  the  shortening  of  the  ventricles  and  retains  the 
apex  in  contact  with  the  chest- wall. 

The  Impulse  or  Apex-beat. — It  must  always  have  been  a  matter  of  com- 
mon knowledge  that,  in  man,  a  portion  of  the  heart  lies  so  close  to  the  chest- 
wall  that,  at  each  beat,  the  soft  parts  of  that  wall  may  be  seen  and  felt  to  pul- 
sate over  a  limited  area.  This  is  commonly  in  the  fourth  or  fifth  intercostal 
space,  midway  between  the  left  margin  of  the  sternum  and  a  vertical  line  let 
fall  from  the  left  nipple.  A  similar  pulsation  maybe  observed  in  other  mam- 
mals. The  protrusion  of  the  chest-wall  at  the  site  of  this  "  impulse  "  or  "apex- 
beat  "  occurs  when  the  arteries  expand,  and  the  up-stroke  of  their  pulse  is  felt  ; 
and  the  recession  of  the  chest  coincides  with  the  shrinking  of  the  arteries  away 
from  the  finger.  The  impulse  proper,  that  is  the  protrusion  of  the  chest-wall, 
occurs,  therefore,  at  the  time  of  the  systole  of  the  ventricles.  By  far  the  most 
important  factor  of  the  apex-beat  is  probably  the  effort  of  the  hardening  ven- 
tricles to  change  the  direction  of  their  long  axis  against  the  resistance  of  the 
chest-wall.  A  heart  severed  from  the  body  and  bloodless,  if  laid  upon  a 
table,  lifts  its  apex  as  it  hardens  in  systole  and  assumes  its  proper  form.  If  a 
finger  be  placed  near  enough  to  the  rising  apex  to  be  struck  by  it,  the  same 
sensation  is  received  as  from  the  impulse. 

It  is  interesting  to  note  that  around  the  point  where  the  soft  parts  of  the 
chest  are  protruded  by  the  impulse,  they  are  found  to  be  very  slightly  drawn 
in  at  the  time  of  its  occurrence.  This  drawing-in  is  called  the  "negative 
impulse,"  and  must  be  caused  by  the  diminution  in  size  of  the  contracting 
ventricles.  These  are  air-tight  within  the  chest,  and  so  their  forcibly  lessened 
surface  must  be  followed  down,  in  varying  degrees,  under  the  pressure  of 
the  atmosphere,  by  the  elastic  and  yielding  lungs  and  by  the  far  less  yield- 
ing soft  parts  of  the  chest-wall. 

The  apex-beat  can  be  brought  to  bear  in  various  ways  upon  a  recording 
lever,  and  thus  be  made  to  inscribe  upon  the  kymograph  a  rhythmically  fluc- 
tuating trace,  which  is  called  a  cardiogram.     Considerable  attention  has  been 

1  J.  B.  Haycraft:  he.  cit.  ~  Haycrafi  :  lot.  cit. 


118  AN    AMERICAN    TEXT- BOOK    OF  PHYSIOLOGY. 

given   to  the  elucidation  of  the  curve  thus  recorded  ;  but,  so  far,  too  little 
agreement  lm<  been  reached  for  the  subject  to  be  entered  upon  here.1 

J.  The  Sounds  of  the  Heart. 

If  the  ear  be  applied  to  the  human  chest,  at  or  near  the  place  of  the  apex- 
beat,  the  heart's  pulsation  will  lie  heard  as  well  as  felt.  This  fact  was  known 
to  Harvey.2  About  two  hundred  years  later  than  Harvey,  in  1819,  the 
French  physician  Laennec,  the  inventor  of  auscultation,  made  known  the  fact 
that  each  heat  of  the  heart  is  accompanied  not  by  one  but  by  two  separate 
sounds.  He  also  called  attention  to  their  great  importance  in  the  diagnosis  of 
the  diseases  of  the  heart;1 

Relations  of  the  Sounds. — The  first  sound  is  heard  during  the  time  when 
the  apex-beat  is  felt  ;  it  therefore  coincides  with  the  systole  of  the  ventricles. 
The  second  sound  is  much  shorter,  and  follows  the  first  immediately,  or,  to 
speak  more  strictly,  after  a  scarcely  appreciable  interval.  The  second  sound, 
therefore,  coincides  with  the  earlier  part  of  the  diastole  of  the  ventricles. 
The  second  sound  is  followed  in  its  turn  by  a  period  of  silence,  commonly 
longer  considerably  than  the  second  sound,  which  silence  lasts  till  the  begin- 
ning of  the  first  sound  of  the  next  ventricular  beat.  The  period  of  silence, 
therefore,  coincides  with  the  later,  and  usually  longer,  portion  of  the  diastole 
of  the  ventricles,  and  with  the  systole  of  the  auricles.  It  is  interesting  that 
the  great  auscultator,  Laennec,  offered  no  explanation  of  the  cause  of  either 
sound,  while  he  made  and  reiterated  the  incorrect  and  misleading  statement 
that  the  second  sound  coincides  with  the  systole  of  the  auricles.  When  the 
heart  beats  oftener  than  usual,  each  beat  must  be  accomplished  in  a  shorter 
time;  and  it  is  found  that,  during  a  briefer  beat,  the  period  of  silence  is 
shortened  much  more  than  the  period  during  which  the  two  sounds  are  audi- 
ble; which  latter  period  may  not  be  altered  appreciably. 

Characters  of  the  Sounds. — The  first  sound  is  not  only  comparatively 
long,  but  is  low-pitched  and  muffled.  The  second  sound  is  comparatively 
short,  and  is  high  and  clear.  The  two  sounds,  therefore,  are  sharply  con- 
trasted in  duration,  pitch,  and  quality.  A  rough  notion  of  the  contrasted 
characters  of  the  sound-  may  lie  obtained  by  pronouncing  the  meaningless 
syllables  "  lubb  dup."  In  other  mammals  the  sounds  have  substantially  the 
same  characters  as  in  man. 

Cause  of  the  Second  Sound. — Since  Laennec's  time,  the  cause  of  the 
-econd  sound  has  been  demonstrated  by  experiment.  The  second  sound  is  due 
to  the  vibrations  caused  by  the  simultaneous  closure  of  the  semilunar  valves 
of  the  pulmonary  artery  and  of  the  aorta,  when  the  diastole  of  the  ventricles 
has   jusi    begun.      This  cause   was   first  suggested  by   the  French   physician 

1  M.  von  Frey  :  Die  Unter&uchung  des  Pulses,  etc.,  1892,  S.  102;  R.  Tigerstedt:  Lehrbuch  der 
Physiologu  d,.<  k'nixlmi/,*,  Leipzig,  1893,  S.  112. 

'-'  Exercilatio  Anatomica  dt  Molv  Cordis  el  Sanguinis  in  Aiiiiindilni.<,  1028,  p.  30;  Willis's  trans- 
lation, Bowie's  edition,  1889,  p.  34. 

3  R.  T.  II.  Lai-nnec:   De  ["auscultation  mediate, etc.,  Paris,  1819. 


CIRCULATION.  119 

Roaa.net  in  1832  j1  not  long  afterward  it  was  conclusively  proven  by  experi- 
ment by  the  English  physician  C.  J.  B.  Williams.2 

Dr.  Williams's  experiment  was  as  follows:  In  a  young  ass  the  chest  was 
opened  and  the  heart  was  exposed.  It  was  ascertained  thai  tin-  second  sound 
was  audible  through  a  stethoscope  applied  to  the  heart  itself.  A  sharp  hook 
was  then  passed  through  the  wall  of  the  pulmonary  artery,  and  was  so  directed 
as  to  make  the  semilunar  valve  incompetent  temporarily.  By  means  of  a 
second  hook,  the  aortic  semilunar  valve  was  likewise  made  incompetent. 
When  both  hooks  were  in  position,  the  heart  was  auscultated  afresh,  and  the 
second  sound  was  found  to  have  disappeared,  and  to  be  replaced  by  a  hissing 
murmur.  The  hooks  were  withdrawn  during  auscultation,  and  at  the  moment 
of  withdrawal  the  murmur  disappeared  and  the  normal  second  sound  recurred. 
Subsequent  clinical  and  post-mortem  observations  have  shown  that  the  second 
sound  may  be  altered  by  disease  which  cripples  the  aortic  valves. 

Causes  of  the  First  Sound. — The  causes  of  the  first  sound  have  not 
been  proven  so  clearly  by  the  available  evidence,  which  is  partly  experimental 
and  partly  derived  from  physical  diagnosis  followed  by  post-mortem  verifica- 
tion. The  first  sound,  like  the  second,  was  ascribed  by  Rouanet3  to  vibrations 
depending  upon  valvular  closure, — the  simultaneous  closure  of  the  tricuspid 
and  mitral  valves ;  but  the  persistence  of  the  sound  throughout  the  whole 
ventricular  systole  made  this  cause  less  probable  than  in  the  case  of  the  second 
sound.  Williams,4  on  the  other  hand,  ascribed  the  first  sound  to  the  con- 
traction of  the  muscular  tissue  of  the  ventricles, — an  explanation  consistent 
with  the  muffled  quality  of  the  first  sound,  and  with  its  persistence  through- 
out the  systole  of  the  ventricles.  It  is  now  believed  by  many  that  both  of 
the  foregoing  explanations  are  correct,  and  that  the  first  sound  is  composite  in 
its  origin,  and  due  both  to  closure  of  the  valves  and  to  muscular  contraction. 
The  evidence  in  favor  of  these  causes  is,  briefly,  as  follows: 

In  favor  of  a  valvular  element  in  the  first  sound,  it  is  maintained  :  Thai 
if  the  ventricles  of  a  dead  heart  be  suddenly  distended  with  liquid,  the  mitral 
and  tricuspid  valves  produce  a  sound  in  closing  ;  and  that  clinical  and  post- 
mortem observations  show  that  the  first  sound  may  lie  altered  by  disease 
which  cripples  the  auriculo-ventricular   valves. 

In  favor  of  an  element  in  the  first  sound  caused  by  muscular  contraction 
it  is  maintained:  That  in  a  still  living  but  excised  heart,  the  first  sound  con 
tinues  to  be  heard  under  circumstances  which  preclude  the  closure  and  vibra- 
tion of  the  valves,  and  leave  in  operation  no  conceivable  cause  for  ilic  first 
sound  except  muscular  contraction.  Experiments  upon  the  first  sound  of 
the  excised    heart    were   reported    in    L868    by  Ludwig  and    Dogiel,8  and    were 

1  J.  Rouanet  :   Analyse  dee  bruits  du  run,-,  Paris,  L8S2. 

2  C.  J.  B.  Williams:  Die  Pathologie  mid  Diagnose  der  Krankheiten  der  Brust,  •<<■.  Nach  der 
dritten,  sehr  vermehrten  Auflage  aus  dem  Englischen  iibersetzt,  Bonn,  1838.  The  writer  baa 
not  seen  an  English  edition.)                                                  3  L<«\  <-i/.  '  /.,„■.  ril. 

3  J.  Dogiel  und  C.  Ludwig:  "Ein  neuer  Versuch  iiber  den  ersten  FTerzton,"  Berichte  £t&< r 
die  Verhandlungen  der  k.  siichsischen  Qesellschafi  der  Wissensehaften  w  Leipzig,  math.-physisehe 
<  tasse,  1868,  S.  89. 


120  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

performed  upon  the  dog  as  follows:  The  heart  was  exposed  daring  arti- 
ficial respiration,  and  loose  ligatures  were  placed  upon  the  venae  cavae,  the 
pulmonary  artery,  the  pulmonary  veins,  and  the  aorta.  Next,  the  loose 
ligatures  were  tightened  in  the  order  above  written,  during  which  process 
the  beating  heart  necessarily  pumped  itself  as  free  as  possible  of  blood. 
The  vessels  were  then  divided  distally  to  the  ligatures,  and  the  heart  was 
excised  and  suspended  in  a  conical  glass  vessel  containing  freshly  drawn  defi- 
brinated  blood,  in  which  the  hearl  was  fully  immersed  without  touching  the 
glass  at  any  point.  Under  these  conditions  the  excised  heart  might  execute 
as  many  as  thirty  beats.  The  conical  glass  vessel  was  supported  in  a  "  ring- 
stand."  The  narrow  bottom  of  the  vessel  consisted  of  a  thin  sheet  of  india- 
rubber,  with  which  last  was  connected  the  flexible  tube  and  ear-piece  of  a 
stethoscope.  By  means  of  the  latter  any  sound  produced  by  the  beating 
heart  could  be  heard  through  the  blood  and  the  sheet  of  rubber.  The  second 
sound  was  not  heard  ;  but  at  each  contraction  of  the  ventricles  the  first  sound 
was  heard,  not  of  the  same  length  or  loudness  as  normally,  but  otherwise  unal- 
tered. The  conditions  of  experiment  were  held  to  preclude  error  resulting 
from  adventitious  sounds ;  moreover,  the  heart  before  excision  had  pumped 
itself  tree  from  all  but  a  fraction  of  the  amount  of  blood  required  to  close  the 
valves,  and  had  been  so  treated  that  no  more  could  enter.  It  was  therefore 
believed  to  be  practically  impossible  that  the  sound  heard  could  have  its 
origin  at  the  valves;  and  no  origin  remained  conceivable  other  than  in  the 
muscular  contraction  of  the  ventricular  systole.  Later  experiments,  in  which 
the  auriculo-ventricular  valves  have  been  rendered  incompetent  by  mechani- 
cal means,  have  seemed  to  confirm  the  importance  of  muscular  contraction  as 
a  cause  of  the  first  sound.1 

By  the  use  of  a  stethoscope  combined  with  a  peculiar  resonator,  the  Ger- 
man physician  Wintrich  of  Erlangen2  satisfied  himself  that  he  could  analyze 
the  first  sound  upon  auscultation,  so  as  to  detect  in  it  two  components,  one 
higher  pitched,  which  he  attributed  to  the  vibration  of  the  auriculo-ventricular 
valves,  and  a  component  of  lower  pitch,  attributed  to  the  muscular  contrac- 
tion df  the  heart.  The  other  experiments  above  referred  to,  however,  which 
sustain  muscular  contraction  as  a  cause  of  the  first  sound,  did  not  reveal  a 
change  of  pitch  following  incompetence  of  the  valves,  but  only  a  diminution 
in  loudness  and  duration. 

Both  the  closure  of  the  cuspid  valves  and  the  contraction  of  the  muscular 
tissue  of  the  ventricles  are  rejected  by  a  recent  observer  as  causes  of  the  first 
sound,  which  he  ascribes  to  the  opening  of  the  semilunar  valves.5 

1  L.  Krehl:  ''  Ueber  den  Herzmuskelton,"  Archiv  fur  Anatomie  und  Physiologic,  Physiolo- 
gische  Ahtheilung,  1889,  8.  253  :  A  Kasem-Bek  :  "  IJeber  die  Kntstebung  des  ersten  Herztones," 
/'    ger1 8  Archiv  fur  die  gesammtt   Physiologic,  L890,  Bd.  xlvii.  8. 53. 

1  Wintrich :  " Experimentalstudien  iiber  Resonanzbewegungen  der  Membranen,"  Sitzwngs- 
phys.-med.  Societal  eu  Erlangen,  1st.!;  Wintrich:  "  Ueber  Causation  und  Analyse 
der  Iler/.etune,"  Ibid.,  1875. 

■'■  K.  Quain:   "On  tbe  Mechanism  by  which  tbe  First  Sound  of  the  Heart  is  Produced," 
lings  of  the  Royal  Society,  vol.  lxi.  p.  331. 


(  [RCULATION.  121 

K.  The  Frequency  op  the  Cardiac  Cycles.1 
In  a  healthy  full-grown  man,  resting  quietly  in  the  sitting  posture,  the 
heart  beats  on  the  average  about  72  times  a  minute.  In  the  full-grown 
woman  the  average  is  slightly  higher,  perhaps  80  to  the  minute.  The  heart 
beats  less  frequently  in  tall  people  than  in  short  ones.  The  difference  between 
men  and  women  largely  depends  upon  this,  but  careful  observation  shows  that 
in  the  case  of  men  and  women  of  the  same  stature  the  heart-beats  are  slightly 
more  frequent  in  the  women.  There  is,  therefore,  a  real  difference  as  to  the 
pulse  between  the  sexes.  Shortly  before  and  after  birth  the  heart-beats  are 
very  frequent,  from  120  to  140  to  the  minute.  During  childhood  and  youth, 
the  frequency  diminishes  gradually,  the  average  falling  below  100  to  the  min- 
ute at  about  the  sixth  year,  and  below  80  to  the  minute  at  about  the  eighteenth 
year.  In  extreme  old  age  the  pulse  becomes  slightly  increased  in  frequency. 
It  must,  however,  be  borne  in  mind  that  there  are  very  wide  differences 
between  individuals  as  to  the  average  frequency  of  the  heart-beats.  Pulses 
of  40  and  even  fewer  strokes  to  the  minute,  or,  on  the  other  hand,  of  more 
than  400  to  the  minute,  are  natural  to  some  healthy  people. 

In  every  individual  the  frequency  of  the  pulse  varies  decidedly,  and  may 
vary  very  greatly,  during  each  twenty-four  hours.  It  is  least  during  sleep, 
aud  less  in  the  lying  than  in  the  sitting  posture.  Standing  makes  the  heart 
beat  oftener,  the  difference  being  greater  between  standing  and  sitting  than 
between  sitting  aud  lying.  During  muscular  exercise  the  pulse-rate  is  much 
increased,  violent  exercise  carrying  it  possibly  to  150  or  even  more.  Thermal 
influences  have  a  marked  effect,  a  hot  bath,  for  instance,  heightening  the  fre- 
quency of  the  pulse  and  a  cold  bath  diminishing  it.  The  taking  of  a  meal 
also  commonly  puts  up  the  frequency.  The  influence  of  emotion  upon  the 
heart's  contractions  is  well  known.  It  may  act  either  to  heighten  the  rate  or 
to  lower  it,  Finally,  the  practising  physician  soon  learns  that  the  heart's 
rate  is  more  easily  affected  by  comparatively  slight  causes,  emotional  or  other- 
wise, in  women,  and  especially  in  children,  than  in  men — a  fact  of  some 
importance  in  diagnosis. 

The  causes  of  the  differences  referred  to  in  this  section  are  partly  unknown, 
and  partly  belong  to  the  subject  of  the  regulation  of  the  circulation. 

L.   The  Relations  in  Time  of  the  Main  Events  of  the  Cardiac 

Cycle. 
We  have  now  considered  the  effects  produced  by  the  cardiac  pump;  its 
general  mode  of  working  ;  and  the  actual  frequency  of  its  strokes.  We  mnsl 
next  studv  certain  important  details  relating  to  the  individual  strokes  or  beats 
of  the  ventricles  and  of  the  auricles.  For  this  study  the  basis  has  already 
been  laid  in  the  sections  headed  "Causes  of  the  Blood-flow  "  (p.  77),  "  Mode 
of  Working  of  the  Pumping  Mechanism"  (p.  78),  "The  Cardiac  Cycle" 
(p.  104),  and  "  Use  and  Importance  of  the  Valves"  (p.   108).      These  sections 

1  Tigerstedt :  Lehrbuch  der  Physiologic  dea  Kreuloufes,  Leipzig,  1898,  8    25  36;  Vierordt: 

Daten  und  Tabellen  zum  Gebrauche  fur  Medieiner,  1888,    fci.  105-109,  'J.">9. 


122  AN   AMERICAN   TEXT-BOOK    OF   PHYSIOLOGY. 

should  now  l>e  read  again  iu  the  order  just  given.  Details  can  best  be  dealt 
with  if  we  use,  instead  of  the  more  familiar  word  "beat,"  the  more  technical 
one  '•  cycle." 

The  Auricular  Cycle  ;  the  Ventricular  Cycle  ;  the  Cardiac  Cycle. — 
Kadi  systole  and  succeeding  diastole  of"  the  auricles  constitute  a  regularly 
recurring  pair  of  events  which  may  truly  be  spoken  of  as  an  "auricular 
cycle  :"  and  SO  also  it  i-  exact  to  say  that  the  ventricles  have  their  cycle,  eon- 
si-ting  of  systole  and  succeeding  diastole.  As  soon,  however,  as  we  strive  for 
clearness,  we  find  that  the  useful  phrase  "cardiac  cycle"  is  necessarily  arbi- 
trary and  imperfect.  A  perusal  of  the  account  given  on  p.  78  of  the  "Mode 
of  Working  of  the  Pumping  Mechanism  "  shows  at  once  that  each  auricular 
cycle,  consisting  of  systole  followed  by  diastole,  must  begiu  shortly  before 
the  corresponding  ventricular  cycle  begins,  and  must  eud  shortly  before  the 
corresponding  ventricular  cycle  ends.  The  pumping  mechanism  is  such  that 
the  auricular  systole  is  completed  just  before  the  ventricular  systole  begins. 
The  phrase  "cardiac  cycle"  implies  a  reference  to  both  auricular  and  ven- 
tricular events  ;  if  now  we  assume  that  the  beginning  of  the  auricular  sys- 
tole marks  the  beginning  of  the  cardiac  cycle,  this  must  eud  either  with  the 
end  of  the  auricular  diastole  or  with  the  eud  of  the  ventricular  diastole.  In 
the  former  case  the  cardiac  cycle  would  coincide  with  the  auricular  cycle,  but 
would  begin  before  the  end  of  one  ventricular  diastole  and  would  end  before 
the  end  of  another,  thus  containing  no  one  complete  ventricular  diastole.  Iu 
the  second  case,  the  cardiac  cycle  would  contain  one  complete  ventricular  dias- 
tole and  a  fraction  of  another,  and  would  also  contain  two  auricular  sys- 
toles. The  second  case  is  clearly  even  more  objectionable  than  the  first.  The 
cardiac  cycle  had  best  be  defined  as  consisting  of  all  the  events  both  auricular 
and  ventricular  which  occur  during  one  complete  auricular  cycle.  The  above 
discussion  deals  with  a  phrase  which  is  a  constant  stumbling-block  to  stu- 
dents; and  the  question  may  well  be  asked,  Why  should  the  expression 
"cardiac  cycle"  not  be  abolished?  The  answer  is,  that  this  phrase  is  indis- 
pensable in  order  to  accentuate  certain  important  relations  of  the  auricular 
cycle  to  the  ventricular.  During  a  heart-beat  there  is  a  period  when  the 
auricles  and  ventricles  are  in  diastole  at  the  same  time.  During  this  period, 
as  we  have  seen,  blood  is  passing  from  the  veins  directly  through  the  auricles 
into  the  ventricles,  and  all  the  muscular  fibres  of  the  heart  are  resting.  This 
period  is  therefore  called  that  of  "the  repose  of  the  whole  heart,"  or  the 
"  pause."  Whenever  the  heart  is  not  wholly  at  rest,  either  auricles  or  ven- 
tricles must  be  in  systole.  We  see,  therefore,  that  each  cardiac  cycle  must 
coincide  with  an  auricular  systole,  the  instantly  succeeding  ventricular  systole, 
and  a  period  of  repose  of  the  whole  heart;  and  it  Is  precisely  these  two 
systoles  and  the  succeeding  universal  rest  which  most  engage  the  attention 
when  the  beating  heart  is  looked  at  in  the  opened  chest.  These  three 
phenomena,  it  will  be  noted,  exactly  coincide  with  one  complete  auricular 
cycle,  and  so  do  not  confuse  the  definition  of  the  cardiac  cycle  which  has  been 
given  already.     We  see,  therefore,  that  the  phrase  which  seemed  at  first  so 


CIU  CULA  TION.  1 23 

misleading  has  a  real  value,  and  will  cease  to  confuse  if  its  limitations  be  care- 
fully noted. 

The  Brevity  and  Variability  of  Each  Cycle. — From  the  frequency  with 
which  the  cycles  recur,  it  follows  at  once  that  each  one,  with  its  complex 
changes  in  the  walls,  chambers,  and  valves,  is  very  rapidly  performed.  If,  for 
instance,  the  heart  beat  72  times  in  one  minute,  each  cycle  occupies  onlv  a 
little  more  than  0.83  of  a  second.  The  brevity  of  each  cycle  is  both  an  im- 
portant physiological  fact  and  a  cause  of  difficulty  in  studying  details.  Each 
cycle,  however,  necessarily  is  capable  of  completion  in  much  less  time  if  the 
pulse-rate  rise  ;  for  instance,  during  exercise.  If  repeated  144  times  a  minute 
instead  of  72  times,  each  cycle  would  occupy  only  one-half  of  its  previous 
time  of  completion.  With  a  pulse  of  less  than  60,  again,  each  cycle  would 
occupy  over  one  second. 

Relative  Lengths  of  the  Ventricular  Systole  and  Diastole. — An  im- 
portant question  is  whether  or  no  there  is  any  fixed  relation  between  the  time 
required  for  a  systole  of  the  ventricles  and  the  time  required  for  a  diastole. 
When  the  length  of  the  cycle  changes  from  one  second  to  one-half  a  second, 
will  the  length  of  the  systole  be  diminished  by  one-half,  and  that  of  the  dias- 
tole also  by  one-half?  Or  is  a  nearly  invariable  time  required  for  the  ventri- 
cles to  do  their  work  of  ejection,  while  the  period  of  rest  and  of  receiving  blood 
can  be  greatly  shortened,  for  a  while  at  least?  The  answer  is  that,  while  both 
systole  and  diastole  may  vary  in  length,  the  length  of  the  systole  is  much  the 
less  variable,  while  the  diastole  is  greatly  shortened  or  lengthened  according  as 
the  heart  beats  often  or  seldom. 

These  facts  have  been  ascertained  as  follows:  A  trained  observer1  auscul- 
tated the  sounds  of  the  human  heart  during  a  number  of  cycles,  and,  at  the 
instant  when  he  heard  the  beginning  either  of  the  first  or  of  the  second  sound, 
made  a  mark  upon  the  revolving  drum  of  a  kymograph  by  means  of  a  sig- 
nalling apparatus.  Of  course,  careful  account  was  taken  of  the  time  lost 
between  the  occurrence  of  a  sound  and  the  recording  of  it.  It  was  found 
that  the  time  between  the  beginning  of  the  first  and  that  of  the  second 
sound  did  not  vary  to  the  same  degree  as  the  frequency  of  the  beats. 
Although  the  interval  in  question  may  not  be  an  exact  measure  of  the 
period  of  ventricular  systole,  it  is  sufficiently  near  it  for  the  purposes  of  this 
observation. 

A  second  method2  depended  upon  the  interpretation  of  the  curve  inscribed 
by  a  lever  pressed  upon  the  skin  over  a  pulsating  human  artery.  Such  a  curve 
exhibits  two  sudden  changes  of  direction,  which  were  taken  to  indicate  approxi- 
mately the  beginning  and  end  of  the  injection  of  blood  by  the  ventricle,  and, 
therefore,  to  afford  a  rough  measure  of  the  duration  of  its  systole.  \\  bile  the 
interpretation  of  the  curve  in  question  is  not  wholly  settled,  it  seems,  aeverthe- 

1  F.  C.  Donders:  "  De  Rhytlmuis  der  Hartetoonen,"  Nederla/ndsch  Archief  -  <n 

Natuurkunde,  1865,  p.  141. 

2  E.  Thurston  :  "The  Length  <>t'  the  Systole  of  the  Heart  as  Intimated  from  Sphygrnogrnphic 
Tracings,"  Journal  of  Anatomy  and  Physiology,  ls7t>,  vol.  x.  p.  494. 


124  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

less,  i"  give  a  fair  basis  for  conclusions  as  to  the  present  question.  The  figures 
resulting  from  the  second  method  are  especially  instructive.  It  was  found  that, 
with  a  pulse  of  47  to  the  minute,  the  approximate  length  of  the  ventricular 
systole  was  0.347  of  a  second  ;  of  the  diastole,  0.930  of  a  second.  With  a 
pulse  of  128  to  the  minute,  while  the  systole  was  only  moderately  diminished, 
viz.  to  0.256  of  a  second,  the  diastole  was  reduced  to  0.213  of  a  second — an 
enormous  decline. 

These  results  upon  the  human  subject  have  been  confirmed  upon  animals 
by  experiments  in  which  were  registered  the  movements  of  a  lever  laid  across 
the  exposed  heart; '  or  the  fluctuations  of  the  pressures  within  the  ventricles.2 

By  whatever  means  investigated,  the  ventricular  systole  is  found  to  be 
shortened  with  the  cycle,  and  to  be  lengthened  with  it;  the  diastole  is  short- 
ened or  lengthened  much  more,  however.  In  fact,  if  the  pulse  become  very 
frequent,  the  diastole  may  be  so  shortened  that  the  "  pause "  nearly  disap- 
pears, and  the  systole  of  the  auricles  follows  speedily  after  the  opening  of 
the  cuspid  valves.  This  signifies  that,  for  a  time,  the  cardiac  muscle  can  do 
with  very  little  rest,  and  that  effective  means  exist  for  a  very  rapid  "charg- 
ing" of  the  ventricular  cavity  when  necessary.  For  the  working  period  of 
the  ventricle,  however,  a  more  uniform  time  is  required.  For  the  average 
human  pulse-rate  this  time  of  work  is  decidedly  shorter  than  the  time  of 
rest — viz.  about  0.3  of  a  second  for  the  former  as  against  about  0.5  for  the 
latter. 

Lengths  of  Auricular  Events  and  of  the  Pause. — The  systole  of  the 
auricles  is  very  brief,  being  commonly  reckoned  at  about  0.1  of  a  second,  as 
the  result  of  various  observations.3  At  the  average  pulse-rate,  therefore,  the 
auricular  systole  is  only  about  one-third  as  long  as  the  ventricular,  and  the 
length  of  the  auricular  diastole  is  to  that  of  the  ventricular  as  seven  to  five. 
Consequently,  a  cardiac  cycle  of  0.8  of  a  second  would  comprise  an  auricular 
systole  of  0.1  of  a  second  ;  a  ventricular  systole  of  0.3  of  a  second ;  and  a 
pause,  or  repose  of  the  whole  heart,  of  0.4  of  a  second — one-half  of  the  cycle. 

Practical  Application. — The  observations  above  described  upon  the  inter- 
val between  the  beginnings  of  the  sounds  have  a  practical  bearing  upon  physical 
diagnosis;  for  they  show  how  faulty  are  the  statements  often  made  which 
assign  regular  proportions  to  the  lengths  of  the  sounds  and  the  silences  of  the 
heart.  The  length  of  the  "second  silence"  must  be  very  fluctuating,  as  it 
comprises  the  longer  part  of  the  fluctuating  ventricular  diastole.  The  length 
of  the  first  sound  and  of  the  very  brief  first  silence  together  must  be  very  con- 
stant, as  they  nearly  coincide  with  the  ventricular  systole. 

1  N.  Baxt:  "Die  Verkurzun^  der  Systolenzeit  durch  den  Nervus  accelerans  cordis,"  Archiv 
fir  Anatomie  wnd  Physiologic,  Physiologische  Abtheilung,  1878,  8.122. 

:  M.  von  l'rey  and  L.  Krelil :  "  Untersuchunffen  fiber  den  Puis,"  Archiv  fiir  Anatomie  und 
Physiologie,  Physiologische  Abtheilung,  1890,  S.  31.  W.T.Porter:  "  Researches  on  the  Filling 
of  the  Heart,"  Journal  uf  Physiology,  1892,  vol.  xiii.  p.  ">.">1. 

II.  Vierordl :   Daien  tmd  Tabellen  mm  Gebrauchefiir  Mediciner,  18S8,  S.  105 


CIRCULATION.  125 

M.     The   Pressures  within  the  Ventricles.' 
We  must  now  approach  the  study  of  further  details  of  the  working  of  the 
ventricular  pumps,  which  details  depend  for  their  elucidation  upon  the  measur- 
ing and  recording  of  the  pressures  within  the  ventricles. 

Absolute  Range  of  Pressure  -within  the  Ventricles  and  its  Signifi- 
cance.— In  dealing  with  the  work  done  by  the  contracting  ventricles  (p.  106) 
we  have  seen  that  the  mercurial  manometer,  as  used  for  studying  the  pressure 
within  the  arteries,  is  quite  unable  to  follow  the  changes  of  the  intra-ventric- 
ular  pressure;  but  that,  by  the  intercalation  of  a  valve,  this  instrument  can  he 
converted  into  a  useful  "  maximum  manometer"  for  the  measuring:  and  record- 
ing  of  the  highest  pressure  occurring  within  the  ventricle  during  a  given  time 
— that  is,  during  a  certain  number  of  cycles.  It  must  now  be  added  that  by  a 
simple  change  of  valves  this  same  instrument  can  at  any  moment  be  changed 
into  a  "minimum  manometer."2  We  can  thus,  by  means  of  the  modified  mer- 
curial manometer,  learn  with  fair  correctness  the  extreme  range  of  pressure 
within  the  ventricles.  As  instances  of  the  extent  of  this  range,  two  observa- 
tions may  be  cited  upon  the  left  ventricle  of  the  dog,  the  chest  not  having  been 
opened.  In  one  animal  the  maximum  was  found  to  be  234  millimeters  of  mer- 
cury, the  maximum  pressure  in  the  aorta  being  212  millimeters;  and  the  min- 
imum in  the  left  ventricle  was  —38  millimeters — that  is  to  say,  38  millimeters 
less  than  the  pressure  of  the  atmosphere,  the  minimum  pressure  in  the  aorta 

1  The  matters  connected  witli  the  ventricular  pressure-curve  may  best  be  studied  in  the  fol- 
lowing writings,  in  which  citations  of  other  papers  maybe  found:  K.  Hiirthle,  in  Pfluger's 
Archiv  fiir  die  gesammte  Physiologie,  as  follows:  "  Zur  Technik  der  Untersuchung  des  Blut- 
druckes,"  1888,  Bd.  43,  S.  399.  "Technische  Mittheilungen,"  1X90,  Bd.  47,  S.  1.  "Ueber 
den  Ursprungsort  der  sekundiiren  Wellen  der  Pulscurve,"  Bd.  47,  S.  17.  "Technische  Mit- 
theilungen," 1891,  I'd.  49,  S.  29.  "  Ueber  den  Zusammenhang  zwischen  Herzthatigkeit  nnd 
Palsform,"  Bd.  49,  S.  51.  "  Kritik  des  Lufttransmissionsverfahrens,"  1*92,  Bd.  5:>,  S.  281. 
''  Vergleichende  Priifung  der  Tonographen  von  Frey's  nnd  Hiirthle's,"  1893,  Bd.  55,  8.  319. 
J.  A.  Tschuewsky  :  "  Vergleichende  Bestimmung  der  Angaben  des  Quecksilber — nnd  des  Feder- 
Manometers  in  Bezugaufden  mittleren  Blutdnick,"  Pfluger's  Archiv fiir  du  gesammte  Physiologic, 
1898,  Bd.  Ixxii.  S.  585.  "Technische  Mittheilungen,"  Ibid.,  1898,  Bd.  lxxii.S.566.  K.  Hiirthle: 
"  ( >rientirungsversuche  iiber  die  Wirkung  des  Oxyspartein  auf  das  I  [erz,  .  I  rchivfiir  experimenteUe 
Pathologie  wnd  Pharmakologie,  1892,  Bd.  xxx.  S.  141.  \V.  I'.  Porter:  "Researches  on  the 
Filling  of  the  Heart."  The  Journal  of  Physiology,  1892,  vol.  xiii.  p.  513.  "A  New  Method  for 
the  Study  of  the  Intracardiac  Pressure  Curve,"  Journal  of  Experimental  Medicine,  L896a  vol.  i.. 
No.  2.  M.  von  Frey  und  L.  Krehl  :  "  Untersuchungen  iiber  den  Puis,"  Archiv  fiir  Anaiom.it  und 
Physiologie,  Physiologische  Abtheilung,  1890,  S.  31.  M.  von  Frey:  "Die  Untersuchung  des 
Pulses,"  Berlin,  1892.  "Das  Plateau  des  Kammerpulses,"  Archiv  fiir  Anatomie  und  Phynolagie, 
Physiologische  Abtheilung,  L893,  S.  1.  "Die  Ermittlung  absoluter  Werthe  fiir  die  Leistung 
von  Pulsschreibern,"  Archiv  fiir  Anatomie  und  Physiologie,  Physiologische  Abtheilung,  1893,  S. 
17.  "  Zur  Theorie  der  Lufttonographen,"  Archiv  fiir  Anaiomie  und  Physiologie,  Physiologische 
Abtheilung,  1893,  S.  204.  "  Die  Erwarmung  der  Full  in  Tonographen,"  Qmtralblatt  fur  Ph 
wlogie  vom  30  Juni,  1894,  Heft  7.  <  >.  Frank:  " Ein  experimentelles  rlilfsmittel  fiir  Eine 
Kritik  der  Karamerdruckcurven,"  Zeitschrifi  fiir  Biologie,  1897,  Bd.  sxxv  8  178.  B.  Rub- 
brecht:  "Recherches  cardiograph iques  chez  les  Oiseaux,"  Archives  de  Biologie,  1898,  t.  w.  p. 
<i47.     .!.  Waroux  :  "  Du  trace*  myograph iqne  due  cceur  exsangue,"  Ibid.,  1898,  t.  sv.  p.  661. 

2 F.  Goltz  und  J.  Gaule :  "  Ueber  die  Druckverhaltnisse  iin  [nnern  des  Herzens,"  Pfluger's 
Archiv  fiir  die  gesammte  Physiologie,  1878,  wii.  S.  100. 


126  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

being  120  millimeters.  In  a  second  dog  the  figures  were  176  and  —30  milli- 
meters for  the  ventricle,  the  aortic  range  being  from  158  to  112  millimeters.1 
In  the  right  ventricle  of  the  dog  such  ranges  as  from  26  to  --8  millimeters, 
from  72  to  —25,  and  various  intermediate  values,  have  been  noted,  both  in 
the  unopened  and  the  opened  chest.2  For  reasons  already  stated  (p.  103)  no 
trustworthy  figures  can  be  given  for  the  pressures  in  the  pulmonary  artery ; 
but  they  can  never  fail  to  be  less  than  the  highest  pressures  within  the  right 
ventricle. 

The  range  of  pressure,  therefore,  within  either  ventricle  is  in  sharp  contrast 
to  that  within  the  artery  which  it  supplies  with  blood;  for  the  arterial  pressure, 
although  it  fluctuates,  is  at  all  times  far  above  that  of  the  atmosphere,  and  is 
able,  as  we  have  seen,  to  maintain  the  circulation  while  the  semilunar  valve  is 
closed  and  the  ventricular  muscle  is  at  rest.  On  the  other  hand,  the  pressure 
within  the  ventricle,  when  at  its  highest,  rises  decidedly  above  the  highest 
arterial  pressure,  and  thus  the  ventricle  can  overcome  this  and  other  opposing 
forces,  open  the  valve,  and  expel  the  blood.  These  facts  have  been  stated 
already.  In  falling,  however,  the  pressure  within  the  ventricle  not  only  sinks 
below  that  in  the  artery,  and  so  permits  the  semilunar  valve  to  close,  but 
sweeps  downward  to  a  point,  it  may  be,  below  the  pressure  of  the  atmosphere, 
and,  in  so  doing,  falls  below  the  pressure  in  the  auricle,  and  permits  the  open- 
ing of  the  auriculo- ventricular  valve  and  the  entrance  of  blood  out  of  the 
auricle  and  the  veins.  As  such  a  great  range  of  pressure  occurs  in  either 
ventricle  of  a  heart  which  is  repeating  its  cycles  with  entire  regularity,  it  is 
presumable  that  at  every  cycle  the  pressure  not  only  rises  above  that  in  the 
arteries  but  may  sink  below  that  of  the  atmosphere. 

Methods  of  Recording  the  Course  of  the  Ventricular  Pressure. — It 
now  becomes  of  interest  to  ascertain,  if  possible,  not  only  the  range,  but  the 
exact  course,  of  these  swift  variations  of  pressure ;  the  causes  of  them,  and  the 
effects  which  accompany  them.  It  is  hard  to  obtain,  by  the  graphic  method,  a 
correct  curve  of  the  pressure  within  either  ventricle.  We  have  seen  that  the 
mercurial  manometer  is  useless  for  this  purpose;  and  it  is  very  difficult  to 
devise  any  self-registering  manometer  which  shall  truly  keep  pace  with  fluctu- 
ations at  once  so  great  and  so  rapid.  The  true  form  of  this  pressure-curve, 
therefore,  still  is  partially  in  doubt,  and  is  the  subject  of  controversies  which 
largely  resolve  themselves  into  contests  between  rival  instruments.  The 
following  characters  are  common  to  the  manometers  with  which  the  most 
serious  attempts  have  lately  been  made  to  obtain  a  true  and  minute  record  of 
the  fluctuations  of  pressure,  even  if  great  and  rapid,  within  the  heart  or  the 
vessels  (see  Fig.  21  |.  As  in  the  case  of  the  mercurial  manometer,  a  cannula, 
open  at  the  end  and  charged  with  a  fluid  which  checks  the  coagulation  of  the 
blood,  i-  tied  into  a  vessel,  or.  if  the  heart  is  under  observation,  is  passed  down 
into  it  through  an  opening  in  a  jugular  vein  or  a  carotid  artery.     If  the  chest 

1  S.  de  Jager:  "  Ueber  die  Saugkraft  des  Herzens,"  Pfliiger's  Archiv  fitr  die  gesammte  Physi- 
ologic, 18^?,,  Bd.  xxxi.  S.  491. 

-S.  de  Jager:  Loc    fit.,    S.  50fi.  507  ;  Goltz  and  Ciaule:   Loc.  rit.,  S.  106. 


CIRCULA  TION. 


127 


have  been  opened,  the  cannula  may  also  be  passed  into  the  heart  through  a  small 
wound  in  an  auricle  or  even  through  the  Malls  of  the  ventricle  itself.  The  end 
of  the  cannula  which  remains  without  the  animal's  body  is  connected,  air-tight, 
with  a  rigid  tube  of  small,  carefully  chosen  calibre,  and  as  short  as  the  condi- 
tions of  the  experiment  permit.  The  other  end  of  this  tube  is  not,  as  in  the 
mercurial  manometer,  left  as  an  open  mouth,  but  is  connected,  air-tight,  with 
a  very  small  metallic  chamber,  which  constitutes,  practically,  a  dilated  blind 
extremity  of  the  system  formed  by  the  tube  and  the  cannula  together.  The 
roof  of  this  small  metallic  chamber  is  a  highly  elastic  disk  either  of  thin  metal 
or  of  india-rubber.  Except  for  this  small  disk,  all  parts  of  the  chamber,  tube, 
and  cannula  are  rigid.  In  the  instruments  of  some  observers,  the  entire  cavity 
of  the  system  formed  by  the  chamber,  tube,  and  cannula  is  filled  with  liquid, 
viz.  the  solution  which  checks  coagulation.     Other  observers  introduce  this 

Y 


SSL 


Fig.  21.— Diagram  of  the  elastic  manometer:  .4,  auricle;  V,  ventricle ;  D,  drum  of  the  kymograph, 
revolving  in  the  direction  of  the  arrow,  and  covered  with  smoked  paper;  L,  recording  lever  in  contact 
with  the  revolving  drum.  (The  working  details  of  the  instrument  are  suppressed  for  the  sake  of  clear- 
ness.) 

liquid  only  into  the  portion  of  the  system  nearest  the  blood  ;  the  terminal 
chamber,  and  most  of  the  rest  of  the  system,  containing  only  air.  In  every 
case  the  blood  in  the  vessel  or  in  the  heart  is  in  free  communication,  through 
the  mouth  of  the  tied-in  cannula,  with  the  cavity  common  to  the  tubes  and 
to  the  terminal  chamber.  At  every  rise  of  blood-pressure  a  little  blood  enters 
this  cavity,  room  being  made  for  it  by  a  displacement  of  liquid  or  of  air, 
which  in  turn  causes  a  slight  bulging  of  the  elastic  disk.  At  every  fall  of 
blood-pressure  a  little  blood  mixed  with  liquid  leaves  the  tubes  as  the  elastic 
disk  recoils.  If  the  disk  is  of  the  right  elasticity,  its  rise  and  fall  are  directly 
proportional  to  the  rise  and  fall  of  the  blood-pressure,  and  can  be  used  to 
measure  it.  With  the  centre  of  the  disk  is  connected  a  delicate  lever  which 
rises  and  falls  with  the  disk.  The  point  of  this  lever  traces  upon  the 
revolving  drum  of  the  kymograph  a  curve  which  records  the  fluctuations 
of  the  disk  and  therefore  those  of  the  blood-pressure.  The  elastic  disk 
and  the  contents,  together,  of  such  an  apparatus  possess  less  inertia  than  mer- 
cury, and  therefore  follow  far  more  closely  rapid  fluctuations  of  pressure. 
Such  instruments  maybe  called  "elastic  manometers,"  and  are  often  called 
" tonographs,"  i.  e.  "tension-writer-."     They  are  of  several  forms. 


128  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

It  has  been  indicated  already  that  the  pressure  of  the  blood  may  be 
communicated  to  the  disk  of  an  elastic  manometer  either  by  means  of 
liquid  or  of  air.  A  given  series  of  fluctuations  of  blood-pressure  may  yield 
decidedly  different  curves  according  to  the  method  of  "  transmission  "  employed 
to  obtain  them  ;  and  the  controversies  as  to  the  true  form  of  the  endocardiac 
pressure-trace  turn  upon  the  question  whether  such  "transmission  by  air"  or 
"transmission  by  liquid  "  yield  the  truer  curve.  The  objections  to  the  former 
method  depend  upon  the  readier  compressibility  of  air;  the  objections  to  trans- 
mission by  liquid  depend  upon  its  greater  inertia. 

The  General  Characters  of  the  Ventricular  Pressure-curve. — What- 
ever   kind   of  elastic    manometer   and    of  transmission    be    used,    the    curve 

Millimeters  of 
mercury. 

Line  of  atmospheric 
pressure. 

Seconds. 

Fig.  22.— Magnified  curve  of  the  course  of  pressure  within  the  right  ventricle  of  the  dog,  the  chest 
being  open  ;  to  be  read  from  left  to  right.  Recorded  by  the  elastic  manometer,  with  transmission  by  air 
(von  Frey). 

obtained  shows  certain  characters  which  are  recognized  by  all  as  properly 
belonging  to  the  changes  of  pressure  within  the  ventricle,  whether  right  or 
left.  These  general  characters,  moreover,  persist  after  the  opening  of  the 
chest.  They  are  as  follows  (see  Figs.  22,  23,  24) :  The  muscular  con- 
t faction  of  the  systole  begins  quite  suddenly,  and  produces  a  swift  and  ex- 


Liiu  of  atmospheric 

pressure. 


Fig.  23. — Magnified  curve  of  the  course  of  pressure  within  the  left  ventricle  and  the  aorta  of  the 
dog,  tic  chesl  being  open  ;  to  be  read  from  left  t<>  right.  Recorded  simultaneously  by  two  clastic  man- 
rs  with  transmission  by  liquid,  in  both  curves  tin1  ordinates  having  the  same  numbers  have  the 
following  meaning:  l.  the  in- taut  preceding  t lie  closing  of  the  mitral  valve  ;  ■_',  the  opening  of  the  semi- 
lunar  valve;  '■'•,  the  beginning  of  the  "dicrotic  wave."  regarded  as  marking  the  instant  of  closure  of  the 
semilunar  valve:   I.  the  instant  preceding  the  opening  of  the  mitral  valve  (Porter). 

tensive  rise  of  pressure,  marked  in  the  curve  by  a  line  but  slightly  inclined 
from  tin;  vertical.  In  the  same  way  the  fall  of  pressure  is  nearly  as  sudden 
and  as  swift  as  the  rise,  and  perhaps  even  more  extensive.  The  systolic  rise 
begins  at  a  pressure  a  little  above  that  of  the  atmosphere;  the  diastolic  fall 
continues,  toward    its  end.  perhaps,  with  diminishing  rapidity,  till  a  point  is 


CIRCULATION.  129 

reached  often  below  the  pressure  of  the  atmosphere.  The  pressure  then 
rises,  perhaps  continuing  negative  for  a  longer  or  shorter  time,  but  presently 
becoming  equal  to  that  of  the  atmosphere.  Near  this  it  continues,  perhaps 
with  a  gentle  upward  tendency,  until,  near  the  end  of  the  ventricular  diastole, 
the  rise  becomes  more  rapid  to  the  point  at  which  the  succeeding  ventricular 
systole  is  to  begin. 

It  is  the  course  of  the  pressure  between  its  rapid  rise  and  its  rapid  fall  which 
has  been  the  most  disputed.  The  observers  who  employ  manometers  with  liquid 
transmission,  have  so  far  found  that  the  high  swift  rise  at  the  outset  of  the 
systole  is  soon  succeeded  by  a  sudden  change.  According  to  them  the  pressure 
within  the  manometer  now  exhibits  fluctuations  of  greater  or  less  extent  which 
are  due,  partly  at  least,  to  the  inertia  of  the  transmitting  liquid  ;  but,  with  due 
allowance  made  for  these,  the  cardiac  pressure  is  seen  to  maintain  itself  at  a 
high  point  throughout  most  of  the  systole  until  the  rapid  fall  begins.  During 
this  period  of  high  pressure,  the  height  about  which  the  fluctuations  occur  may 
remain  nearly  the  same ;  or  this  height  may  gradually  increase,  or  gradually 
decrease,  up  to  the  beginning  of  the  rapid  fall.  As  is  shown  by  Figure  23, 
this  course  of  the  systolic  pressure  causes  its  curve  to  bend  alternately  down- 
ward and  upward  between  the  end  of  its  greatest  rise  and  the  beginning  of  its 
greatest  fall ;  but  between  these  two  points  the  general  direction  of  the  curve 
approaches  the  horizontal,  and  therefore  entitles  this  portion  of  it  to  the  name 

12  3       4 


M ill i meters  of 
mercury. 


Line  of  atmospheric 
pressure. 


Tenths  of  "  second. 

Fig.  24.— Magnified  curve  of  the  course  of  pressure  within  the  left  ventricle  of  >li<-  dog,  the  chest 
being  open;  to  be  read  from  left  to  right.  Recorded  by  the  elastic  manometer  with  transmission  by  air. 
The  crdinates  have  the  following  meaning:  l,  the  closure  of  the  mitral  valve;  2,  the  opening  oi  the  semi- 
lunar valve ;  3,  the  closure  of  the  semilunar  valve;  I,  the  opening  of  the  mitral  valve  (von  Fr<  j  i. 

of  the  "  systolic  plateau,"  a  name  which  becomes  more  truly  descriptive  when 
appropriate  means  are  taken  to  eliminate  the  fluctuations  due  to  inertia.  The 
best  of  the  manometers  with  air  transmission  yields  a  curve  ot*  the  pressure 
within  the  ventricle  which  presents  a  different  picture  (Figs.  22  and  24). 
The  steeply  rising  line  may  diminish  its  steepness  somewhat  as  it  ascends, 
but  its  rapid  turn  at  the  highest  point  of  the  curve  is  succeeded  by  no  plateau. 
The  line  simply  describes  a  single  peak,  and  begins  the  descent  which  marks 
the  rapid  fall  of  pressure  recognized  by  all  observers.  In  these  peaked  curves 
Vol.  I.— 9 


130  AN  AMERICAN    TENT-BOOK    OE   PHYSIOLOGY. 

this  descent  is  often  steepest  in  its  middle  part.  Such  a  peaked  curve  would 
indicate,  of  course,  that  there  is  no  such  thing  as  the  maintenance,  daring  any 
large  part  of  the  systole  of  the  ventricles,  of  a  varying  but  high  pressure. 
The  experienced  observer  who  is  the  chief  defender  of  the  peaked  curve  holds 
the  plateau  to  be  a  product  either  of  too  much  friction  within  the  manometer 
tubes,  or  of  a  faulty  position  of  the  cannula  within  the  heart,  whereby  com- 
munication with  the  manometer  is,  for  a  time,  cut  off.  The  able  and  more 
numerous  adherents  of  the  plateau,  on  the  other  hand,  attribute  the  failure 
to  obtain  it  to  the  sluggishness  of  the  instrument  employed,  or  to  an  abnor- 
mal condition  of  the  heart.  Recent  comparative  tests  of  elastic  manometers, 
and  other  studies,  would  seem  to  show  that  the  curves  obtained  by  liquid 
transmission,  and  which  exhibit  the  plateau,  afford  a  truer  picture  of  the 
general  course  of  the  pressure  within  the  ventricles  than  the  peaked  curves 
written  by  means  of  air. 

The  Ventricular  Pressure-curve  and  the  Auricular  Systole. — It  is 
striking  testimony  to  the  smoothness  of  working  of  the  cardiac  mechanism, 
that  the  curve  of  intra-ventricular  pressure  rarely  gives  any  clear  indication  of 
the  beginning  or  end  of  the  auricular  systole.  This  event  may  be  expected  to 
increase  the  pit -sure  within  the  ventricles;  and,  in  the  curve,  the  very  gentle 
pise  which  coincides  with  the  latter  and  longer  part  of  the  ventricular  diastole 
passes  into  the  steep  ascent  of  the  commencing  ventricular  systole  by  a 
rounded  sweep,  which  indicates  a  more  rapidly  heightened  pressure  within 
the  ventricle  during  the  auricular  systole.  As  a  rule,  no  angle  reveals  an 
instantaneous  change  of  rate  to  show  the  beginning  or  end  of  the  injection  of 
blood  by  the  contracting  auricle  (see  Figs.  22,  23,  24).  Occasionally,  how- 
ever, a  slight  "  presystolic  "  fluctuation  of  the  curve  may  seem  to  mark  the 
auricular  systole.1 

The  Ventricular  Pressure-curve  and  the  Valve-play. — It  is  also 
exceedingly  striking  that  no  curve,  whether  it  be  pointed  or  show  the  sys- 
tolic plateau,  gives  a  clear  indication  of  the  instant  of  the  closing  or  open- 
ing of  either  valve,  auriculo-ventricular  or  arterial  (see  Figs.  22,  23,  24). 
These  instants,  so  important  for  the  significance  of  the  curve,  can,  however, 
be  marked  upon  it  after  they  have  been  ascertained  indirectly.  A  method 
of  general  application  would  be  as  follows:  Two  elastic  manometers  are 
"absolutely  graduated  "  by  causing  each  of  them  to  record  a  series  of  pressures 
already  measured  by  a  mercurial  manometer.  The  two  elastic  manometers  can 
tlnn  be  made  to  mark  upon  the  same  revolving  drum  the  simultaneous  changes 
of  pressure  in  a  ventricle  and  in  its  auricle,  or  in  a  ventricle  and  its  artery. 
The  pressure  indicated  by  any  point  of  either  curve  can  then  be  calculated 
in  terms  of  millimeter-  of  mercury.  That  point  upon  the  intra-ventricular 
curve  which  marks  a  rising  pressure  just  higher  than  the  simultaneous  pressure 
in  the  auricle  or  artery,  may  be  taken  to  mark  the  closing  of  the  cuspid  valve 
or  the  opening  of  the  semilunar  valve,  as  the  case  may  be.  By  a  converse 
process,  the  moment  of  opening  of  the  cuspid  valve,  or  of  closing  of  the  semi- 
1  von  Frey  and  Krehl:  op.  cit.,  p.  61. 


CIRCULATION. 


131 


lunar,  may  also  be  ascertained.  The  practical  difficulties  in  the  way  of 
applying-  this  method  to  the  ventricle  and  auricle  are  much  greater  than  to  the 
ventricle  and  artery.  By  another  application  of  the  principle  just  described,  a 
"differential  manometer"  has  been  devised  for  the  purpose  of  registering  as  a 
single  curve  the  successive  differences,  from  moment  to  moment,  between  the 
ventricular  and  auricular  pressures,  or  the  ventricular  and  arterial  pressures 
(see  Fig.  25).  To  this  end,  two  elastic  manometers  are  fastened  immovably 
together,  and  their  two  elastic  disks,  instead  of  bearing  upon  separate  levers, 
are  made  to  bear  upon  a  single  one,  which  has  its  fulcrum  between  the  disks, 
and  is  a  lever  not  of  the  third  order,  but  of  the  first,  like  a  common  balance. 


Fig.  25.— Diagram  of  the  differential  manometer:  A,  artery:  V,  ventricle;  Z>,  drum  of  kymograph, 
revolving  in  the  direction  of  the  arrow,  and  covered  with  smoked  paper;  L,  recording  lever  in  contact 
with  the  revolving  drum ;  8,  a  spring  by  which  the  movement  of  the  lever  worked  by  the  disks  is  trans- 
mitted to  the  recording  lever.  (The  working  details  of  the  instrument  are  suppressed  or  altered  for  the 
sake  of  clearness.) 

As  the  lever  or  beam  of  the  balance  turns  from  the  horizontal  as  soon  as  the 
scales  are  pressed  upon  by  unequal  weights,  so  the  lever  of  the  differential 
manometer  turns  as  soon  as  the  disks  are  unequally  affected  by  the  pressures 
within  the  ventricle  and  the  auricle,  or  the  ventricle  and  the  artery.  As,  how- 
ever, the  pressures  upon  the  scales  are  from  above,  while  those  upon  the  disks 
are  from  below,  the  disk  which  tends  to  "kick  the  beam"  is  the  one  acted 
upon  by  the  greater  pressure,  instead  of  by  the  less,  as  in  the  case  of  the  scales. 
The  manometric  lever  marks  its  oscillations  as  a  curve  upon  the  kymograph 
by  the  help  of  a  second  or"  writing  lever"  connected  with  it.  The  persistence 
of  exactly  equal  pressures,  no  matter  what  their  absolute  value,  in  the  two 
manometers  would  cause  a  horizontal  line  to  be  drawn  by  the  writing  lever. 
This  would  serve  as  a  base-line.  The  differential  manometer  is  ;i  valuable 
instrument,  although  it  is  evident  that  where  such  minute  differences  of  space 
and  time  are  recorded  as  a  curve  by  such  complicated  mechanisms,  the  sources 
of  error  must  be  numerous  and  difficult  to  avoid.1 

The  methods  which  proceed  by  the  measurement  of  differences  of  pressure 
may  sometimes  be  controlled,  or  even  replaced,  by  an  easier  method,  as  follows: 
If  two  manometers  simultaneously  record  on  the  same  kymograph  thepressure- 
1  K.  Hurthle:  Pfluger'a  Arehiv fur  die gesammie  Phyiriologie,  1891,  Bd.  49,  S.  45. 


132  AN   AMERICAN    TEXT-HOOK    OF  PHYSIOLOGY. 

curves  of  the  ventricle  and  the  auricle,  or  of  the  ventricle  and  the  artery,  any 
\v,t  sudden  change  of  pressure,  produced  in  auricle  or  artery  at  the  opening  or 
shutting  of  a  cardiac  valve,  will  produce  a  peak  or  angle  in  the  curve  of  pres- 
sure of  the  auricle  or  artery.  By  the  rules  of  the  graphic  method  the  point  in 
the  pressure-curve  of  the  ventricle  can  easily  be  found  which  was  written  at 
the  same  instant  with  the  peak  or  angle  in  the  auricular  or  arterial  curve. 
That  point  upon  the  ventricular  curve,  when  marked,  will  indicate  the  instant 
of  opening  or  shutting  of  the  valve  in  question.  In  the  pressure-curve  ob- 
tained from  the  aorta  close  to  the  heart,  there  is  a  sudden  angle  which  clearly 
marks  the  instant  when  the  opening  of  the  semilunar  valve  leads  to  the  sudden 
rise  of  pressure  which  causes  the  up-stroke  of  the  pulse  (see  Fig.  23).  Again, 
the  fluctuation  of  aortic  pressure  which  we  shall  learn  to  know  as  the  "dicrotic 
wave"  begins  at  a  moment  which  many  believe  to  follow  closely  upon  the  clos- 
ure of  the  semilunar  valve.  That  moment  may  be  indicated  by  a  notch  in  the 
aortic  curve.  So,  too,  the  rise  of  pressure  within  the  auricle  produced  by  its 
systole  may  suddenly  be  succeeded  by  a  fall,  the  beginning  of  which  must  mark 
the  closure  of  the  cuspid  valve,  which  closure  thus  may  correspond  with  the 
apex  of  the  auricular  curve. 

In  Figure  23,  ordinate  1  indicates  the  closing,  and  ordinate  4  the  open- 
ing, of  the  mitral  valve.  These  two  points  were  found  by  help  of  the  dif- 
ferential manometer.  <  Ordinate  2  indicates  the  opening,  and  ordinate  3  the 
closing,  of  the  aortic  valve.  These  two  points  were  marked  with  the  help 
of  the  curve  of  aortic  pressure,  also  shown  in  Figure  23,  each  ordinate  of 
which  has  the  same  number  as  the  corresponding  ordinate  of  the  ventricular 
curve.  In  the  arterial  curve,  2  marks  the  beginning  of  the  systolic  rise, 
and  3  the  beginning  of  the  dicrotic  wave,  which  latter  point  is  treated  by 
the  observer  as  closely  corresponding  to  the  closure  of  the  aortic  valve.  In 
figure  24  each  ordinate  has  the  same  number,  and,  as  regards  the  valve- 
play,  the  same  significance,  as  in  figure  23.  Ordinate  1  corresponds  to  the 
apex  of  a  peak  in  the  auricular  curve  (not  here  given)  which  represents  the 
end  of  the  auricular  systole.  Ordinate  2  corresponds  to  the  beginning  of  the 
systolic  ascent  in  the  aortic  curve  (not  here  given).  Ordinate  3  was  found 
by  comparing,  by  means  of  two  elastic  manometers,  the  simultaneous  pressures 
in  the  ventricle  and  the  aorta.  Ordinate  4  corresponds,  on  the  auricular 
pressure-curve,  to  a  point  which  marks  the  beginning  of  a  decline  of  pres- 
sure believed  by  the  observer  to  succeed  the  opening  of  the  cuspid  valve.- 
In  both  the  figures  given  of  the  ventricular  curve,  and  in  such  curves 
in  general,  the  points  which  mark  the  valve-play  occur  as  follows:  The 
.closure  of  the  cuspid  valve  corresponds  to  a  point,  not  tar  above  the  line 
<>f  atmospheric  pressure,  where  the  moderate  upward  sweep  of  the  ventric- 
ular curve  takes  on  the  steepness  of  the  systolic  ascent.  The  systole  of  the 
auricle  is  of  little  force,  and  the  blood  injected  by  it  into  the  distensible  ven- 
tricle rai-e-  the  pressure  there  but  little;  that  little,  however,  is  more  than 
the  relaxing  auricle  presents,  and  the  cuspid  valve  is  closed.  Somewhere  on 
the  steep  -ystolie  ascent  occur-  the  point  corresponding  to  the  rise  of  the  ven- 


CIRCULATION.  133 

tricular  above  the  arterial  pressure,  and  therefore  to  the  opening  <>t'  the  semi- 
lunar valve.  But  other  forces  beside  the  arterial  pressure  must  be  overcome 
by  the  contracting  muscle;  and  the  ventricular  pressure  mounts  higher  vet, 
and  either  stays  high  for  a  while,  producing  the  plateau,  or,  in  a  peaked  curve, 
at  once  descends.  In  either  ease,  not  long  after  the  beginning  of  the  sharp 
descent,  the  point  occurs  at  which  the  ventricular  pressure  falls  below  the  arte- 
rial, and  the  semilunar  valve  is  closed.  Beyond  this  point  the  curve  continues 
steeply  downward,  but  it  is  not  till  a  point  is  reached  not  far  above,  or  possibly 
even  below,  the  atmospheric  pressure  that  the  pressure  in  the  ventricle  falls 
below  that  in  the  auricle,  and  the  cuspid  valve  is  opened. 

The  Period  of  Reception,  the  Period  of  Ejection,  and  the  Two  Periods 
of  Complete  Closure  of  the  Ventricle. — During  the  whole  of  the  period 
when  the  cuspid  valve  is  open,  the  pressure  is  lower  in  the  ventricle  than  in 
the  artery ;  the  arterial  valve  is  shut ;  and  blood  is  entering  the  ventricle. 
This  may  be  called  the  "  period  of  reception  of  blood."  During  the  greater 
part  of  the  period  when  the  cuspid  valve  is  shut,  the  arterial  valve  is  open ; 
the  pressure  is  higher  in  the  ventricle  than  in  the  artery;  and  the  ejection 
of  blood  from  the  former  is  taking  place.  This  may  be  called  the  "period 
of  ejection,"  and  lies  in  Figures  23  and  24  between  the  ordinates  2  and 
3.  The  careful  work  which  has  enabled  us  to  mark  the  valve-play  upon 
the  ventricular  curve  has  demonstrated  the  interesting  fact  that  there  occur 
two  brief  periods  during  each  of  which  both  valves  are  shut,  and  the  ven- 
tricle is  a  closed  cavity.  Of  these  two  periods,  one  immediately  precedes  the 
period  of  ejection,  and  the  other  immediately  follows  it.  The  first  lies,  in 
Figures  23  and  24,  between  the  ordinates  1  and  2  ;  the  second,  between  3 
and  4.  The  explanation  of  these  two  periods  is  simple.  It  takes  a  brief  but 
measurable  time  for  the  cardiac  muscle,  forcibly  contracting  upon  the  impris- 
oned liquid  contents  of  the  closed  ventricle,  to  raise  the  pressure  to  the  high 
point  required  to  overcome  the  opposing  pressure  within  the  artery  and  to  open 
the  semilunar  valve.  Again,  it  takes  a  measurable  time,  probably  seldom 
quite  so  brief  as  the  period  just  discussed,  for  the  cardiac  muscle  to  relax  suffi- 
ciently to  permit  the  pressure  in  the  closed  ventricle  to  fall  to  the  low  point 
required  for  the  opening  of  the  cuspid  valve.  The  ventricular  cycle,  thus 
studied,  falls  into  four  periods:  the  first  is  a  brief  period  of  complete  closure 
with  swiftly  rising  pressure;  the  second  is  the  period  of  ejection,  relatively 
long,  and  but  little  variable  ;  the  third  is  a  period  of  complete  closure,  with 
swiftly  falling  pressure;  the  fourth  is  the  period  when  the  pressure  is  low  and 
blood  is  entering  the  ventricle.  This  last  period  is  very  variable  in  length, 
but  at  the  average  pulse-rate  it  is  the  longest  period  of  all. 

Phenomena  of  the  Period  of  Reception  of  Blood. — We  have  already 
followed  the  course  of  the  pressure  within  the  ventricle  from  the  moment  of 
opening  of  the  auriculo-ventrieular  valve  to  that  of  its  closing  (p.  128). 
During  this  time  the  ventricle  is  receiving  its  charge  of  blood,  the  flaccidity  of 
the  wall  rendering  expansion  easy  and  keeping  the  pressure  low.  The  blood 
which  ent<r-  first  has  been  accumulating  in  the  auricle  since  the  closing  of  the 


134  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

cuspid  valve,  and  now,  upon  the  opening  of  this,  it  botli  flows  and  is  to  some 
slight  degree  drawn  into  the  ventricle.  This  blood  is  followed  by  that  which, 
during  the  remainder  of  the  "repose  of  the  whole  heart,"  moves  through  the  veins 
and  the  auricle  into  the  ventricle  under  the  influence  of  the  arterial  recoil  and 
the  other  forces  which  cause  the  venous  flow  (p.  93)  ;  and  the  charge  of  the 
ventricle  is  completed  by  the  blood  which  is  injected  at  the  auricular  systole. 

The  Negative  Pressure  within  the  Ventricles. — That  the  heart,  in  its 
diastole,  draws  something  from  without  into  itself  is  a  very  ancient  belief,  and 
this  mode  of  its  working  played  a  great  part  in  the  doctrines  of  Galen  and  of 
the  Middle  Ages.  In  1543,  Vesalius,  who,  on  anatomical  grounds,  questioned 
some  of  Galen's  views  as  to  the  cardiac  physiology,  fully  accepted  this  one.1 
On  the  other  hand,  in  1628,  Harvey  rejected  it.  "It  is  manifest,"  he  says, 
"  that  the  blood  enter-  the  ventricles  not  by  any  attraction  or  dilatation  of  the 
heart,  but  by  being  thrown  into  them  by  the  pulses  of  the  auricles."  :  In  this 
particular,  modern  research  in  some  degree  confirms  the  opinion  of  the  ancients, 
while  denying  to  suction  within  the  ventricles  any  such  great  effect  as  was 
once  believed  in.  As  a  rule,  the  cuspid  valve  is  not  opened  till  the  pressure  in 
the  ventricle  has  fallen  to  a  point  not  far  from  the  pressure  of  the  atmosphere ; 
it  may  be  even  below  it.  In  any  case  the  ventricular  pressure  usually  becomes 
negative  very  soon  after  the  opening  of  the  cuspid  valve.  This  negative  pres- 
sure is  of  variable  extent  and  continues  for  a  variable  time.  It  is  always 
small  as  compared  with  the  positive  pressure  of  the  systole.  Under 
some  circumstances  negative  pressure  may  be  absent,  but  it  is  so  very  com- 
monly present  as  certainly  to  be  a  normal  phenomenon  (sec  Figs.  22, 
2o,  and  24).  This  negative  pressure  is  revealed  by  the  elastic  as  well 
as  by  the  minimum  mercurial  manometer;  it  is  present  in  both  ventri- 
cles ;  and  it  is  present,  to  a  less  degree,  even  after  the  chest  has  been 
opened,  and  its  aspiration  destroyed.  It  is  in  virtue  of  the  forces  which 
produce  the  negative  pressure  in  the  manometer  that  blood  is  drawn  into 
the   heart. 

Passing  by  disproven  or  improbable  theories  as  to  the  causes  of  this  suction, 
we  -hall  find  the  following  statements  justified:  As  the  heart  lies  between  the 
lungs  and  the  chest-wall  (including  in  this  term  the  diaphragm),  it  is  subject, 
like  the  chest-wall  and  the  great  vessels,  to  the  continuous  aspiration  produced 
by  the  stretched  fibres  of  the  elastic  lungs.  At  every  inspiration  this  aspiration 
is  increased  by  the  contraction  of  the  inspiratory  muscles.  We  see,  therefore, 
that  the  ventricle  must  overcome  this  aspiration  as  part  of  the  resistance  to  its 
contraction;  and  that,  as  soon  as  that  contraction  has  ceased,  the  walls  of  the 
ventricle  must  tend  to  be  drawn  asunder  by  those  same  forces  of  elastic  recoil 
in  the  pulmonary  fibre-,  and  of  contraction  of  the  muscles  of  inspiration,  which 
we  have  -ecu  (p.   95)  to  produce  a  slight  -net  ion  within  the  great  veins  in  and 

1  Andrea  Vescdii  BruxeUensis,  Schola  medicorvm  Patavince  professoris,  <!>■  Humani  corporis 
fabrica  Libri  septan.  Basilese,  ex  officina  [oannis  Oporini,  Anno  Salutie  reparatse  MDXLIIL 
Page  587. 

2  Op.  cit.,  1628,  p.  26:  Willis's  translation,  Bowie's  edition,  1889,  p.  28. 


CIRCULATION.  135 

very  near  the  chest.  These  same  forces  produce  a  slight  suction  within  the 
ventricles,  relaxed  in  their  diastole.  But  a  very  slight  suction  occurs  at  each 
ventricular  diastole  even  after  the  chest  has  been  opened.  The  causes  of  this 
arc  -till  obscure;  but  it  is  to  be  borne  in  mind  that  the  relaxing  wall  of  the 
ventricle,  flabby  as  it  is,  possesses  some  little  elasticity,  especially  at  the  auriculo- 
ventricular  ring,  and  therefore  may  tend  to  resume  a  somewhat  different  form 
from  that  due  to  its  contraction.  As  the  result  of  this  slight  elastic  recoil,  a 
feeble  suction  may  occur. 

N.  The  Functions  of  the  Auricles. 

Connections  of  the  Auricle. — Into  the  right  and  left  auricles  open  the 
systemic  and  pulmonary  veins  respectively,  and  each  auricle  may  justly  be  re- 
garded as  the  enlarged  termination  of  that  venous  system  with  which  it  is  con- 
nected. Until  modern  times  the  terms  of  anatomy  reflected  this  view,  and 
from  the  ancient  Greeks  to  a  time  later  than  Harvey,  the  word  "  heart  "com- 
monly meant  the  ventricles  only,  as  it  still  does  in  the  language  of  the 
slaughter-house.  This  termination  of  the  venous  system,  the  auricle,  com- 
municates directly  with  the  ventricle,  at  the  auriculo-ventrieular  ring,  by  an 
aperture  so  wide  that,  when  the  cuspid  valve  is  freely  open,  auricle  and  ven- 
tricle together  seem  to  form  but  a  single  chamber. 

The  Auricle  a  Feeble  Force-pump  ;  the  Pressure  of  its  Systole. — The 
wall  of  the  auricle  is  thin  and  distensible;  it  is  also  muscular  and  contractile. 
But  the  slightest  inspection  of  the  dead  heart  shows  how  little  force  can  be 
exerted  by  the  contraction  of  so  thin  a  sheet  of  muscle.  In  the  Avail  of  the 
appendix,  however,  the  muscular  structure  is  more  vigorously  developed -than 
over  the  rest  of  the  auricle.  The  auricle,  then,  should  be  a  very  feeble  force- 
pump  ;  and  such  in  fact,  it  is  ;  for  the  highest  pressure  scarcely  rises  above  20 
millimeters  of  mercury  in  the  right  auricle  of  the  dog,1  and  an  auricular  sys- 
tole often  produces  a  pressure  of  only  5  or  10  millimeters.2  This  would  be 
but  a  small  fraction  of  the  maximum  ventricular  pressure  of  the  same  heart. 
The  auricle,  however,  is  equal  to  its  work  of  completing  the  filling  of  the 
ventricle;  and  the  feebleness  of  the  auricle  will  not  surprise  us  when  we 
consider  that,  at  the  beginning  of  its  systole,  the  pressure  exerted  by  the 
contents  of  the  relaxed  ventricle  is  but  little  above  that  of  the  atmosphere, 
and  offers  small  resistance  to  the  injection  of  an  additional  quantity  of 
blood. 

The  systole  of  the  auricles  is  so  conspicuous  a  part  of  the  cardiac  cycle  when 
the  beating  heart  is  looked  at,  that  its  necessity  is  easily  overrated.  Even  Har- 
vey, in  attacking  the  errors  of  his  day,  was  led  by  imperfect  methods  to  estimate 
too  highly  the  work  of  the  auricular  systole  (see  p.  184).  The  error,  although 
a  gross  one,  is  not  rare,  of  considering  the  systole  of  the  auricles  to  be  as  im- 
portant for  the  charging  of  the  ventricles  as  the  systole  of  the  ventricles  is  for 
the  charging  of  the  arteries.      On  page  98  the  proof  has  already  been  given 

1  Goltz  und  <i:iulo:  op.  fit.,  p.  106. 

1  YV.  T.  Porter  :  op.  cit.,  p.  533.    8.  de  Jager  :  op.  <-ii.,  p.  506. 


136  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

that  the  work  of  the  heart  may  entirely  suffice  to  maintain  the  circulation  with- 
out aid  from  any  subsidiary  source  of  energy.  It  must  now  he  added  that  the 
ventricles  can,  for  a  time,  maintain  the  circulation  without  the  aid  of  the  auric- 
ular systole — a  clear  proof  that  this  systole  is  not  a  sine  qua  non  for  the 
working  of  the  cardiac  pump. 

If  in  an  animal,  not  only  anaesthetized  but  so  drugged  that  all  its  skeletal 
muscles  arc  paralyzed,  artificial  respiration  be  established  and  the  chest  be 
opened,  the  circulation  continues.  If  the  artificial  respiration  be  suspended 
for  a  time,  the  lungs  collapse,  asphyxia  begins,  and  the  blood  accumulates 
conspicuously  in  the  veins  and  in  the  heart.  Presently  the  muscular  walls 
of  the  auricles  may  become  paralyzed  by  overdistention,  and  their  systoles 
may  cease,  while  the  ventricles  continue  at  work  and  may  maintain  a  circu- 
lation, although  of  course  an  abnormal  one.  After  the  renewal  of  artificial 
respiration,  it  may  not  be  till  several  beats  of  the  ventricles  have  succeeded, 
without  help  from  the  auricles,  in  unloading  the  latter  and  the  veins,  that  the 
auricles  recommence  their  beats.1 

On  the  other  hand,  it  is  clear  that  the  auricle  is  not  without  importance  as 
a  force-pump  for  completing  the  filling  of  the  ventricle,  even  if  it  can  be  dis- 
pensed with  for  a  time.  In  curves  of  the  blood-pressure  during  asphyxia  taken 
simultaneously  from  the  auricle  and  the  ventricle,  there  may  be  noted  the  influ- 
ence exerted  upon  the  ventricular  curve  by  ineffectiveness  of  the  auricular  sys- 
tole. It  is  found  that,  in  this  ease,  that  slight  but  accelerated  rise  of  pressure 
may  fail  which  normally  just  precedes,  and  merges  itself  in,  the  large  swift  rise 
of  the  ventricular  systole.  It  is  found,  too,  that,  under  these  circumstances, 
the  total  height  of  this  systolic  rise  may  be  diminished.2  We  shall  see  pres- 
ently how,  when  the  pulse  becomes  very  frequent,  the  importance  of  the  auric- 
ular systole  may  be  increased.  We  have  seen  already  (p.  132)  that  normally  it 
may  probably  effect  the  closure  of  the  cuspid  valves. 

Time-relations  of  the  Auricular  Systole  and  Diastole. — The  auricular 
systole  is  not  only  weak,  but  brief,  being  commonly  reckoned  at  about  0.1  of  a 
second  (see  p.  124).  If  this  be  correct  for  man,  at  the  average  pulse-rate  of 
72  the  auricular  systole  would  comprise  only  about  one-eighth  of  the  cycle; 
would  be  only  one-seventh  as  long  as  the  auricular  diastole;  and  only  about 
one-third  as  long  as  the  ventricular  systole  which  immediately  follows  that  of 
the  auricle. 

The  Auricle  a  Mechanism  for  Facilitating  the  Venous  Plow  and 
for  the  "Quick-charging"  of  the  Ventricle. — Further  points  in  regard  to 
the  systole  of  the  auricles  can  best  be  treated  of  incidentally  to  the  general 
question,  What  is  the  principal  use  of  this  portion  of  the  heart?  The  answer 
i-  not  so  obvious  as  in  the  ease  of  the  ventricles.  It  may,  however,  be  stated 
as  follows  :  The  auricle  is  a  reservoir,  lying  at  the  very  door  of  the  ventricle. 
That  door,  the  cuspid  valve,  remains  shut  during  the  relatively  long  and  un- 
varying period  of  the  ventricular  systole  and  the  brief  succeeding  period  of  fall- 

1  veil  Frey  unci  Krehl:  op.  cit.,  pp.  49,59.  G.  Colin:  Train'  </<  plni.<i<>l,>iiif  rompurir  rfrx  ,mi- 
maux,  Paris.  1888,  vol.  ii.  p.  424.  2  von  Frey  und  Krehl:  op.  cil.,  p.  59. 


CIRCULATION.  137 

ing  pressure  within  the  ventricle.  These  periods  coincide  with  the  earlier  part 
of  the  auricular  diastole.  During  all  this  time  the  forces  which  cause  the 
venous  flow  are  delivering  blood  into  the  flaccid  and  distensible  reservoir  of 
the  auricle,  and  can  thus  maintain  a  continuous  flow.  But  the  blood  of  which 
the  veins  are  thus  relieved  during  the  period  of  closure  of  the  cuspid  valve, 
accumulates  just  above  that  valve  to  await  its  opening.  When  it  is  opened 
by  the  superior  auricular  pressure,  the  stored-up  blood  both  flows  and  is  drawn 
into  the  ventricle  promptly  from  the  adjoining  reservoir.  From  this  time 
on,  auricle  and  ventricle  together  are  converted  into  a  common  storehouse  for 
the  returning  blood  during  the  remainder  of  the  repose  of  the  whole  heart, 
which  coincides  with  the  later  portion  of  the  long  auricular  diastole.  The 
next  auricular  systole  completes  the  charging  of  the  ventricle ;  and  a  second 
use  of  this  systole  now  becomes  apparent,  for  the  sudden  transfer  by  it  of 
blood  from  auricle  to  ventricle  not  only  completes  the  filling  of  the  latter,  but 
lessens  the  contents  of  the  auricle,  and  so  prepares  it  to  act  as  a  storehouse 
during  the  coming  systole  of  the  ventricle.  The  auricle,  then,  is  an  apparatus 
for  the  maintenance  of  as  even  a  flow  as  possible  in  the  veins  and  for  the  rapid 
and  thorough  charging  of  the  ventricle.  It  is  clear  that,  for  both  uses,  the 
auricle's  function  as  a  reservoir  is  certainly  no  less  important  than  its  function 
as  a  force-pump. 

The  value  of  a  mechanism  for  the  rapid  filling  of  the  ventricle  increases 
with  the  pulse-rate,  and  with  a  very  frequent  pulse  must  be  of  great  import- 
ance, because  now  time  must  be  saved  at  the  expense  of  the  pause,  with  its 
quiet  flow  of  blood  through  the  auricle  into  the  ventricle ;  and  the  auricular 
systole  must  follow  more  promptly  than  before  upon  the  opening  of  the  cus- 
pid valve.  If  the  pulse  double  in  frequency,  each  cardiac  cycle  must  be  com- 
pleted in  one-half  the  former  time;  but  we  have  seen  that  the  ventricle 
requires  for  its  systole  a  time  which  cannot  be  shortened  with  the  cycle  to  the 
same  degree  as  can  its  diastole.  Of  heightened  value  now  to  the  ventricle 
will  be  the  adjoining  reservoir,  which  is  filling  while  the  cuspid  valve  remains 
closed,  and  from  which,  as  soon  as  that  valve  is  opened,  the  necessary  supply 
not  only  flows,  but  is  sucked  and  pumped  into  the  ventricle,  tor,  when  increased 
demands  are  made  upon  the  heart,  the  usefulness  of  an  increased  frequency  of 
beat  disappears  if  the  volume  transferred  at  each  beat  from  veins  to  arteries 
diminish  in  the  same  proportion  as  the  frequency  increases.  No  increase  of 
the  capillary  stream  can  then  follow  the  more  frequent  strokes  of  the  pump.1 

Negative  Pressure  within  the  Auricle  ;  its  Probable  Usefulness. — The 
course  of  the  pressure-curve  of  the  auricle,  as  shown  by  the  elastic  manome- 
ter, is  too  complex  and  variable,  and  its  details  are  too  much  disputed,  for  it 
to  be  given  here.  But  certain  facts  regarding  the  auricular  pressure  are  of 
much  interest  in  connection  with  the  use  of  the  auricle  which  has  jus!  been 
discussed.  Once,  and  perhaps  oftener,  in  each  cycle,  the  pressure  in  the  auricle 
may  become  negative,  perhaps  to  the  degree  of  from  —2  to— 10  millimeters  of 
mercury  even  in  the  open  chest,-' and  of  course  becomes  still   more  so  when 

1  von  Frey  und  Kivlil ;  op.  tit.,  p.  61. 

2  de  Jager  :  op.  eit.,  p.  507.     W.  T.  Porter:  op.  cit.,  p.  533. 


138  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

the  latter  is  intact,  sinking  in  this  case  to  perhaps— 11.2  millimeters.1  What 
is  striking  in  connection  with  the  "quick -charging'"  of  the  ventricle  is  that 
the  greatest  and  longest  negative  pressure  in  the  auricle  coincides,  as  we  should 
expect,  with  the  earlier  part  <>f  its  diastole,  and  therefore  with  the  systole  of 
the  ventricle,  when  the  auricle  is  cut  off  from  it  by  the  shut  valve.2  By 
this  suction  within  the  auricle  the  flow  from  the  veins  into  it  probably  is 
heightened,  and  the  store  of  blood  increased  which  accumulates  in  the  reservoir 
to  await  the  opening  of  the  valve.  The  quick-charging  mechanism  itself  is 
quickly  charged.  Nor  should  it  be  forgotten  that  the  work  of  the  ventricle 
contributes  in  some  degree  to  this  suction  within  the  auricle.  The  heart  is 
air-tight  in  the  chest,  which  is  a  more  or  less  rigid  case.  At  each  ventricular 
systole  the  heart  pumps  some  blood  out  of  this  case,  and  shrinks  as  it  does  so, 
thus  tending  to  produce  a  vacuum;  in  other  words,  to  increase  the  amount  of 
negative  pressure  within  the  chest,  and  thus  help  to  expand  the  swelling-  auri- 
cles. Therefore  for  the  suction  which  helps  to  charge  the  auricles  during  the 
systole  of  the  ventricles,  that  systole  itself  is  partly  responsible.3 

Is  the  Auricle  Emptied  by  its  Systole  ? — Authorities  differ  still  as  to  the 
extent  to  which  the  auricle  is  emptied  by  its  systole;  some  holding  the  scarcely 
probable  view  that,  during  this  time,  its  contents  are  all,  or  nearly  all,  trans- 
ferred to  the  ventricle;4  and  others  taking  the  widely  different  view  that  the 
auricle  actually  continues  to  receive  blood  during  its  systole,  which  latter  simply 
increases  the  discharge  into  the  ventricle.  According  to  this  latter  opinion  the 
flow  from  the  great  veins  into  the  auricle  is  absolutely  unbroken.5  All  are 
agreed,  however,  that  the  auricular  appendix  is  the  most  completely  emptied 
portion  of  the  chamber. 

Are  the  Venous  Openings  into  the  Auricle  closed  during-  its  Systole  ? 
If  not,  does  Blood  then  regurgitate,  or  enter? — As  to  these  questions  dif- 
ferences of  opinion  are  possible,  because  at  the  openings  of  the  veins  into  the 
auricle  no  valves  exist  which  are  effective  in  the  adult,  except  at  the  mouth  of 
the  coronary  sinus.  It  is  therefore  a  question,  what  happens  at  the  mouths  of 
the  veins  during  the  auricular  systole.  These  mouths  are  surrounded  by  rings 
composed  of  the  muscular  fibres  of  the  auricular  wall ;  and  for  some  distance 
from  the  heart  the  walls  of  some  of  the  great  veins  are  rich  in  circular  fibres 
of  muscle.  We  have  seen  already  (p.  115)  that  a  rhythmic  contraction  of  the 
venae  cavic  and  pulmonary  vein-  occurs  just  before  the  systole  of  the  auricles 
and  musl  accelerate  the  flow  into  the  latter.  Their  swiftly  following  systole  is' 
known  to  begin  at  the  mouths  of  the  great  veins  and  from  these  to  spread  over 
the  rest  of  each  auricle.     It  is  evident  at  once  that  the  circular  fibres  must 

1  <  roltz  and  <  ranle :  op.  cit.,  p.  109. 

2  von  Frey  uud  Krehl:  i>/>.  cit.,  p.  5.",;   \\r.  T.  Porter:  op.  cit.,  p.  523. 

'  A.  Mosso:  Die  Diagnostik  des  Pulses,  etc.  Zweiter  Theil  :  Ueber  den  negativen  Puis, 
S.  42. 

1  M.  Foster:  .1  Text-book  of  Physiology,  New  York,  1896,  p.  182. 

0  Skoda:  "  I'eher  die  Function  der  Vorkammern  des  Herzens,"  Sitzungsberichfe  der  maihem.- 
rmturw.  Classe  der  kai*.  Akminnif  'l<r  Wixsnixchnften  in  Wien,  1852,  Bd.  ix.  S.  788.  L.  Her- 
mann :   Lehrbuch  der  Physiologie,  1900,  S.  66. 


CIRCULATION.  139 

either  narrow  or  obliterate,  like  sphincters,  the  months  of  the  veins  at  the  out- 
set of  the  systole,  and  that  these  fibres  thus  take  the  place  of  valves.  If  the 
closure  be  complete,  all  the  blood  ejected  by  the  systole  mustenter  the  ventricle, 
and  a  momentary  standstill  of  blood  and  rise  of  pressure  in  the  vein-  just  with- 
out the  auricle  must  accompany  its  brief  systole.  A  recent  observer  believes 
the  flow  into  the  auricle  to  be  interrupted  even  more  than  once  during  its  cycle.1 
If  the  venous  openings  be  not  closed  but  only  narrowed  during  the  systole 
of  the  auricles,  the  transfer  of  all  or  most  of  the  ejected  blood  to  the  ventricle 
must  depend  upon  the  pressure  being  lower  therein  than  at  the  venous  openings. 
A  slight  regurgitation  into  the  veins  would,  like  the  complete  closing  of  their 
mouths,  cause  a  momentary  checking  of  their  blood-flow  just  without  the  auri- 
cle, and  a  slight  rise  of  pressure.  Such  a  checking  of  the  flow  has  in  some 
cases  been  observed  and  ascribed  to  regurgitation.2  A  systolic  narrowing  with- 
out closure  of  the  venous  mouths  would  leave  room  also  for  the  view  already 
given,  that  so  far  is  regurgitation  from  taking  place,  that  even  during  the  sys- 
tole of  the  auricles  blood  enters  them  incessantly,  and  the  venous  flow  is  never 
checked.  In  this  case  the  systole  of  the  auricle  would  still  empty  it  partially 
into  the  ventricle,  owing  to  the  lowuess  of  the  pressure  there. 

The  time  has  not  arrived  for  a  decision  as  to  all  these  questions,  which  are 
surrounded  by  practical  difficulties ;  but  fortunately  they  do  not  throw  doubt 
upon  the  functions  of  the  auricle  as  a  reservoir  and  pump  which  may  be 
swiftly  filled,  and  may  swiftly  complete  the  filling  of  the  ventricle  which  it 
adjoins. 

O.  The  Arterial  Pulse. 

Nature  and  Importance. — The  expression  "  arterial  pulse  "  is  restricted 
commonly  to  those  incessant  fluctuations  of  the  arterial  pressure  which  corre- 
spond with  the  incessant  beatings  of  the  ventricles  of  the  heart.  These  rhyth- 
mic fluctuations  of  the  arterial  pressure  have  been  explained  already  (p.  92) 
to  depend  upou  the  rhythmic  intermittent  injections  of  blood  from  the  ven- 
tricles; upon  the  resistance  to  these  injections  produced  by  the  friction  within 
the  blood-vessels;  and  upon  the  elasticity  of  the  arterial  walls.  It  ha-  also 
been  explained  that  the  interaction  of  these  three  factors  is  Mich  that  the  blood, 
in  traversing  the  capillaries,  comes  to  exert  a  continuous  pressure,  free  from 
rhythmic  fluctuations;  in  other  words,  that  the  pulse  undergoes  extinction  :it 
the  confines  of  the  arterial  system.  It  is  at  once  apparent  that  the  pulse  may 
be  affected  by  an  abnormal  change,  either  in  the  heart's  heat,  in  the  elas- 
ticity of  the  arteries,  or  in  the  peripheral  resistance,  or  by  a  combination 
of  such  changes;  and  that,  therefore,  the  character-  of  the  pulse  possess 
an  importance  in  medical  diagnosis  which  justifies  a  brief  further  discus- 
sion of  them. 

A  pulsating  artery  not  only  expands,  but  is  lengthened.     The  sudden 

1  W.  T.  Porter :  op.  cil.,  p.  534. 

*  Francois-Franck :  "Variations  de  la  viteeae  du  Bang  dana  !«'s  veines  sous  ['influence 
de  la  svstole  de  l'oreillette  droite,"  Archives  <!•■  physiologie  normale  >t  pathologique,  1890,  \>.  •">!:. 


140  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

increase  in  the  contents  of  an  artery  which  causes  the  pulse  therein,  is  accom- 
modated not  merely  by  the  increase  of  calibre  which  produces  the  "  up-stroke " 
of  the  arterial  wall  against  the  finger,  but  also  by  an  increase  in  the  length 
df  the  elastic  vessel.  If  the  artery  be  sinuous  in  its  course,  this  increase  in 
length  suddenly  exaggerates  the  curves  of  the  vessel,  and  thus  produces  a 
slight  wriggling  movement.  This  is  sometimes  very  clearly  visible  in  the 
temporal  arteries  of  emaciated  persons.  On  the  other  hand,  the  increase  in 
the  calibre  of  the  artery  is  relatively  so  slight  that  it  is  invisible  at  the  profile 
even  of  a  large  artery,  dissected  clean  for  a  short  distance  for  the  purpose  of 
tying  it.  Such  a  vessel  appears  pulseless  to  the  eye,  although  its  pulse  is 
easilv  felt  by  the  finger,  which  slightly  flattens  the  artery  and  thus  gains  a 
larger  surface  (if  contact. 

Transmission  of  the  Pulse. — If  an  observer  feel  his  own  pulse,  placing 
the  finger  of  one  hand  upon  the  common  carotid  artery,  and  that  of  the  other 
upon  the  dorsal  artery  of  the  foot  at  the  instep,  he  will  perceive  that  the  pulse 
corresponding  to  a  given  heart-beat  occurs  later  in  the  foot  than  in  the  neck. 
This  phenomenon  is  readily  comprehended  by  considering  that  room  for  the 
"  pulse-volume  "  injected  by  the  heart  is  made  in  the  root  of  the  arterial  system 
both  by  local  expansion  and  by  a  more  rapid  displacement  of  blood  into  the 
next  arterial  segment.  This  next  segment,  in  turn,  accommodates  its  increased 
charge  by  local  expansion  and  by  a  more  rapid  displacement ;  and  this  same 
process  involves  segment  after  segment  in  succession,  onward  toward  the 
capillaries.  The  expansion  of  the  arterial  system,  then,  is  a  progressive  one, 
and,  as  the  phrase  is,  spreads  as  a  wave  from  the  aorta  onward  to  the  arteri- 
oles. The  rate  of  transmission  of  the  "pulse-wave"  from  a  point  near  the 
heart  to  one  remote  from  it,  may  be  calculated.  This  is  done  by  comparing 
the  time  which  elapses  between  the  occurrence  of  the  up-stroke  of  the  pulse 
in  the  nearer  and  in  the  farther  artery  with  the  distance  along  the  arterial 
system  which  separates  the  two  points  of  observation.  In  one  case,  for  exam- 
ple, that  of  an  adult,  the  absolute  amount  of  the  postponement  of  the  pulse — 
that  is,  the  time  required  for  the  transmission  of  the  pulse-wave  from  the 
heart  itself  to  the  arteria  dorsalis  pedis,  was  0.193  second.1  The  time  of 
transmission  of  the  pulse-wave  from  the  heart  to  the  dorsalis  pedis  is  often 
longer  than  in  this  case,  amounting  to  0.2  second  or  a  little  more.  If  we 
reckon  the  duration  of  the  ventricular  systole  at  about  0.3  second,  it  is  evi- 
dent that  the  fact  of  the  postponement  of  the  pulse  in  the  arteries  distant  from 
the  heart  does  not  invalidate  the  general  statement  that  the  arterial  pulse  is 
synchronous  with  the  systole  of  the  ventricles. 

The  general  estimates  of  the  rate,  as  opposed  to  the  absolute  time,  of  trans- 
mission of  the  pulse-wave  vary,  in  different  cases,  from  more  than  3  meters 
to  more  than  !)  meters  per  second.  As  the  blood  in  the  arteries  does  not  pass 
onward  at  a  -witter  rate  than  about  0.5  meter  per  second,  it  is  clear  that  the 
wave  of  expansion  moves  along  the  artery  many  times  faster  than  the  blood 
does  ;  and  that  t<>  confound  the  travelling  of  the  wave  with  the  travelling  of 
1  J.  N.  Czermak:  Gcsamm.Uc  Schrifim,  1S79,  Bd.  i.  Abth.  2,  8.  711. 


CIRCULATION.  141 

the  blood  would  be  a  very  serious  error,  easily  avoided  by  bearing  in  mind 
the  causes  of  the  pulse-wave  as  already  given. 

Investigation  by  the  Finger. — The  feeling  of  the  pulse  has  beeD  a  valu- 
able and  constantly  used  means  of  diagnosis  since  ancient  times.  Indeed,  the 
ancient  medicine  attached  to  it  more  importance  than  does  the  practice  of 
to-day.  But  it  is  still  advisable  to  warn  the  beginner  that  he  may  not  look 
to  the  pulse  for  "pathognomonic"  information  ;  that  is  to  say,  he  may  not 
expect  to  diagnosticate  a  disease  solely  by  touching  an  artery  of  the  patient 
under  examination.  The  pulse  is  most  commonly  felt  in  the  radial  artery, 
which  is  convenient,  superficial,  and  well  supported  against  an  examining 
finger  by  the  underlying  bone.  Many  other  arteries,  however,  may  be  util- 
ized. 

Frequency  and  Regularity. — The  most  conspicuous  qualities  of  the  pulse 
are  frequency  and  regularity.  Usually  these  can  be  appreciated  not  merely  by 
a  physician  but  by  any  intelligent  person.  The  physiological  variations  in 
the  frequency  of  the  heart's  beats  have  been  referred  to  already  (p.  121).  In 
an  intermittent  pulse  the  rhythm  is  usually  regular,  but,  at  longer  or  shorter 
intervals,  the  ventricle  omits  a  systole,  and  therefore,  the  pulse  omits  an  up- 
stroke. Either  intermittence  or  irregularity  of  the  cardiac  beats  may  be 
caused  by  transient  disorder  as  well  as  by  serious  disease. 

Tension. — When  unusual  force  is  required  in  order  to  extinguish  the  pulse 
by  compressing  the  artery  against  the  bone,  the  arterial  wall,  and  hence  the 
pulse,  is  said  to  possess  high  tension,  or  the  pulse  is  called  incompressible,  or 
hard.  Conversely,  the  pulse  is  said  to  be  of  low  tension,  compressible,  or  soft, 
when  its  obliteration  is  unusually  easy.  A  very  hard  pulse  is  sometimes  called 
"wiry;"  a  very  soft  one,  "gaseous."  High  tension,  hardness,  incompressibil- 
ity,  obviously  are  directly  indicative  of  a  high  blood-pressure  in  the  artery  ; 
and  the  converse  qualities  of  a  low  pressure.  It  follows  from  what  has  gone 
before  that  the  causes  of  changes  in  the  arterial  pressure,  and  hence  in  the 
tension,  may  be  found  in  changes  either  in  the  heart's  action,  or  in  the  periph- 
eral resistance,  or,  as  is  very  common,  in  both.  An  instrument  called  a 
sphygmomanometer1  or  sphygmometer  is  sometimes  applied  to  the  skin  over 
the  artery,  in  order  to  obtain  a  better  measurement  of  its  hardness  or  softness, 
and  hence  of  the  blood-pressure  within  it,  than  the  finger  can  make.  Such 
instruments  are  not  free  from  sources  of  error. 

Size. — When  the  artery  is  unusually  increased  in  calibre  at  each  up-stroke 
of  the  pulse,  the  pulse  is  said  to  be  large.  When,  at  the  up-stroke,  the  calibre 
changes  but  little,  the  pulse  is  said  to  be  small.  A  very  large  pulse  is  some- 
times called  "bounding;"  a  very  -mall  one,  "  thready."  Largeness  of  the 
pulse  must  be  distinguished  carefully  from  largeness  of  the  artery.  The  for- 
mer phrase  means  that  the  fluctuating  pari  of  the  arterial  pressure  is  large 
in  proportion  to  the  mean  pressure.  But  if  the  mean  pressure  be  great 
while  the  fluctuating  part  of  the  pressure  i-  relatively  small,  the  artery,  even 
at  the  end  of  the  down-stroke,  will  be  of  large  calibre,  while  the  pulse  will 

be  small. 

'  From  r<  >v)  u6i ,  pulse. 


142  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

It  has  been  seen  that  the  increased  charge  of  blood  which  an  artery  receives 
at  the  ventricular  systole  is  accommodated  partly  by  increased  displacement  of 
blood  toward  the  capillaries,  and  partly  by  that  increase  in  the  capacity  of  the 
artery  which  is  accompanied  by  the  up-stroke  of  the  pulse.  The  less  the  con- 
tents of  the  artery  the  less  is  the  arterial  pressure,  the  less  the  tension  of  the 
wall,  and  the  more  yielding  is  that  wall.  The  more  yielding  the  wall,  the  more 
of  the  increased  charge  of  blood  does  the  artery  accommodate  by  an  increase  of 
capacity  and  the  less  by  an  increase  of  displacement.  Therefore,  a  large  pulse 
often  accompanies  a  low  mean  pressure  in  the  arteries,  and  hence  may  appear 
as  a  symptom  after  large  losses  of  blood.  In  former  days,  when  bloodletting 
was  practised  as  a  remedial  measure,  imperfect  knowledge  of  the  mechanics 
of  the  circulation  sometimes  caused  life  to  be  endangered  ;  for  a  "throbbing" 
pulse  in  a  patient  who  had  been  bled  already  was  liable  to  be  taken  as  an  "in- 
dication" for  the  letting  of  more  blood.  If  this  were  done,  an  effect  was 
combated   by   repeating  its  cause.1 

Celerity  of  Stroke. — When  each  up-stroke  of  the  pulse  appears  to  be 
slowly  accomplished,  requiring  a  relatively  long  interval  of  time,  the  pulse 
is  called  slow,  or  long.  When  each  up-stroke  appears  to  be  quickly  accom- 
plished, requiring  a  relatively  short  time,  the  pulse  is  called  quick  or  short. 
These  contrasted  qualities  are  among  the  most  obscure  of  those  which  the 
skilled  touch  is  called  upon  to  appreciate. 

The  Pulse-trace. — The  rise  and  fall  of  a  pulsating  human  artery,  if  near 
enough  to  the  skin,  may  be  made  to  raise  and  lower  the  recording  lever  of  a 
somewhat  complicated  instrument  called  a  sphygmograph.2  Of  this  instru- 
ment a  number  of  varieties  are  in  use.  If  the  fine  point  of  the  lever  be  kept 
in  contact  with  a  piece  of  smoked  paper  which  is  in  uniform  motion,  a  "pulse- 
trace"  or  "pulse-curve"  is  inscribed,  which  shows  successive  fluctuations, 
larger  and  smaller,  which  tend  to  be  rhythmically  repeated,  and  which  depend 
upon  the  movements  of  the  arterial  wall  produced  by  the  fluctuations  of  blood- 
pressure.  In  an  animal,  a  manometer  may  be  connected  with  the  interior  of 
an  artery,  and  thus  the  fluctuations  of  the  blood-pressure  may  be  observed 
more  directly.  It  has  been  explained  (p.  90)  that  the  mercurial  manometer 
is  of  no  value  for  the  study  of  the  finer  characters  of  the  pulse,  owing  to 
the  inertia  of  the  mercury.  On  the  other  hand,  the  best  forms  of  elastic 
manometer  give  pulse-traces  which  are  more  reliable  than  those  of  the  sphyg- 
mograph. This  is  because  the  sphygmographic  trace  is  subject  to  unavoid- 
able errors  dependent  upon  the  physical  qualities  of  the  skin  and  other 
parts  which  intervene  between  the  instrument  and  the  cavity  of  the  artery. 
Nevertheless,  the  sphygmographic  pulse-trace,  or  "  sphygmogram,"  is  the 
only  pulse-trace  which  can  be  obtained  from  the  human  subject;  and,  when 
obtained  from  an  animal,  it  has  so  much  in  common  with  the  trace  recorded 
by  the  elastic  manometer,  that  the  sphygmograph  has  been  much  used  for  the 
Study  of  the  human  pulse,  in  health  and  disease,  both  by  physiologists  and  by 

1  Marshall  Hall:  Researches  principally  relative  to  the  Morbid  and  Ourative  Effects  of  Loss  of 
Blood,  London,  1830.  2  From  a<pvyfi6c,  pulse,  and  ypacpetv,  to  record. 


CIRCULATION.  143 

medical  practitioners.  As  a  means  of  diagnosis,  however,  the  sphygmogram 
still  leaves  much  to  be  desired.  The  same  instrument,  applied  in  immediate 
succession  to  different  arteries  of  the  same  person,  gives,  as  might  be  expected, 
pulse-traces  of  somewhat  different  forms.  The  same  artery  of  the  same  per- 
son yields  to  the  same  instrument  at  different  times  different  forms  of  trace, 
depending  upon  different  physiological  states  of  the  circulation.  But  the  same 
artery  yields  traces  of  different  form  to  sphygmographs  of  different  varieties 
applied  to  it  in  immediate  succession;  and  even  moderate  changes  in  adjust- 
ment cause  differences  in  the  form  of  the  successive  traces  which  the  same 
instrument  obtains  from  the  same  artery.  It  is  no  wonder,  therefore,  that 
great  care  must  be  exercised  in  comparing  sphygmographic  observations,  and 
in  drawing  general  conclusions  from  the  information  which  they  impart. 

The  Details  of  the  Sphygmogram. — Figure  26  is  a  fair  example  of 
the  sphygmograms  commonly  obtained  from  the  healthy  human  radial  pulse. 
When  this  trace  was  taken,  the  subject's  heart  was  beating  from  58  to  GO  times 


Fig.  26. — Sphygmogram  from  a  normal  human  radial  pulse  beating  from  58  to  60  times  a  minute.    To  be 
read  from  left  to  right  (Burdon-Sanderson). 

a  minute.  The  trace  records  the  effects  upon  the  lever  of  five  successive  com- 
plete pulsations  of  the  artery,  which  all  agree  in  the  general  character  of  their 
details,  while  differing  in  minor  respects.  By  the  tracing  of  each  pulsation 
the  up-stroke  is  shown  to  be  sudden,  brief,  and  steady,  while  the  down-stroke 
is  gradual,  protracted,  and  oscillating.  The  commencing  recoil  of  the  arterial 
wall  succeeds  its  expansion  with  some  suddenness.  In  many  sphygmograms 
this  is  exaggerated  by  the  inertia  of  the  instrument.  As  shown  by  the  t  race  rep- 
resented in  the  figure,  and  by  most  such  traces,  the  recoil  soon  changes  from 
rapid  to  gradual,  and,  in  the  trace,  its  protracted  line  becomes  wavy,  indicating 
that  the  slow  diminution  of  calibre  varies  its  rate,  or  even  is  interrupted  by  one 
or  more  slight  expansions,  before  it  reaches  its  lowest,  and  is  succeeded  by  the 
up-stroke  of  the  next  pulsation.  In  each  of  the  five  successive  pulsations  the 
traces  of  which  are  shown  in  Figure  26,  the  line  which  represents  the  more 
gradual  portion  of  the  down-stroke  of  the  pulse  is  made  up  of  three  waves, 
of  which  the  first  is  the  shortest,  the  last  the  longest  and  lowest,  and  the  mid- 
dle one  intermediate  in  length,  but  by  far  the  highest.  This  middle  wave  is, 
in  fact,  the  only  one  of  the  three  to  produce  which  an  actual  pise  of  pressure 
occurs ;  in  each  of  the  other  two,  no  rise,  bul  only  a  diminished  rate  of  decline, 
is  exhibited.  The  changes  of  pressure  which  produce  the  first  aud  third  of 
the  waves  jusl  spoken  of,  in  the  pulse-trace  under  consideration,  are  very 
obscure  in  their  origin, and  are  inconstanl  in  their  occurrence, sometimes  being 
more  numerous  than  in  the  trace  shown  in  Fig.  26,  and  sometimes  failing 
altogether  to  appear. 

The  Dicrotic  Wave. — The  oscillation  of  pressure,  however,  which  pro- 


144  AN   AMERICAN    TEXT-HOOK   OF   PHYSIOLOGY. 

duces  the  middle  wave  of  each  of  the  pulsations  of  Figure  26,  is  so  constant 
in  its  occurrence  that  it  is  undoubtedly  a  normal  and  important  phenomenon, 
although,  in  different  sphygmograms,  the  height,  and  position  in  the  trace,  of 
the  wave  inscribed  by  this  oscillation  may  vary.  Occasionally  this  oscillation 
is  morbidly  exaggerated,  so  thai  it  may  be  not  only  recorded  by  the  sphygmo- 
graph,  but  even  felt  by  the  finger,  as  a  second  usually  smaller  up-stroke  of 
the  pulse.  In  such  a  ease  the  artery  is  felt  to  beat  twice  at  each  single  beat 
of  the  ventricle, and  is  said,  technically,  to  show  a  "dicrotic"1  pulse.  Where 
a  dicrotic  pulse  cau  be  detected  by  the  finger,  it  is  apt  to  accompany  a  mark- 
edly low  menu  tension  of  the  arterial  wall.  The  dicrotic  pulse  was  known, 
and  named,  long  before  the  sphygmograph  revealed  the  fact  that  the  pulse  is 
always  dicrotic,  although  to  a  degree  normally  too  slight  for  the  linger  to 
appreciate.  The  sphygmographic  wave  which  records  the  slight  "dicrotism  " 
of  the  normal  pulse  is  called  the  "  dicrotic  wave."  Where  dicrotism  can  be 
felt  bv  the  finger,  the  sphygmogram  naturally  exhibits  a  very  conspicuous 
dicrotic  wave. 

The  origin  of  the  dicrotic  oscillation  has  been  much  discussed,  and  is  not 
vet  thoroughly  settled,  important  as  a  complete  settlement  of  it  would  be  to 
the  true  interpretation  and  clinical  usefulness  of  the  sphygmogram.  It  is 
believed  bv  some  that  this  fluctuation  of  pressure  is  produced  at  the  smaller 
arterial  branches,  as  a  reflection  of  the  main  pulse-wave,  and  that  the  dicrotic 
wave,  thus  reflected,  travels  toward  the  heart,  and,  naturally,  reaches  a  given 
artery  after  the  main  wave  of  the  pulse  has  passed  over  it,  travelling  in  the 
opposite  direction.  The  weight  of  probability,  however,  is  in  favor  of  the 
view  that  the  dicrotic  wave  essentially  depends  upon  a  slight  rise  of  the 
arterial  pressure,  or  slackening  of  its  decline,  due  to  the  closing  of  the  semi- 
lunar valve  ;  and  that,  therefore,  this  wave  follows  the  main  wave  of  arterial 
expansion  outward  from  the  heart,  instead  of  being  reflected  inward  from  the 
periphery.  If  the  dicrotic  wave  be  caused  solely  by  reflection  from  the 
periphery,  it  ought,  in  a  sphygmogram  from  a  peripheral  artery,  to  begin  at 
a  point  nearer  to  the  highest  point  of  each  pulsation  than  in  the  case  of  an 
artery  near  the  heart,  in  which  latter  vessel,  naturally,  a  reflected  wave  would 
undergo  postponement.  On  the  other  hand,  if  the  dicrotic  wave  be  trans- 
mitted toward  the  periphery,  and  caused  solely  by  the  closure  of  the  aortic 
valve,  it  ought,  in  a  sphygmogram  from  a  peripheral  artery,  to  occupy  very 

nearly  the  sa relative  position  as  in  a  sphygmogram  taken  from  an  artery 

Dear  the  heart.  But  a  wave  running  toward  the  periphery  may  be  modified 
by  a  reflected  wave  in  the  same  vessel,  and  a  reflected  wave  may  undergo  a 
second  reflection  at  the  closed  aortic  valve,  or  even  elsewhere,  and  thus  give 
rise  to  an  oscillation  which  will  he  transmitted  toward  the  periphery.  These 
statements  show  with  what  technical  difficulties  the  subject  is  beset,  whether 
the  sphygmograph  be  employed,  or,  in  the  case  of  animals,  the  elastic  man- 
ometer, the  traces  recorded   by    which   also   exhibit   the  dicrotic  wave.     As 

1  From  iViKporcic,  double-beating. 


CIR  C  ULA  TIOX.  1 45 

already  stated,  however,  the  probabilities  are  in  favor  of  the  valvular  origin 
of  the  dicrotic  wave. 

If  it  be  true  that  the  closure  of  the  aortic  valve  causes  the  dicrotic  wave, 
the  instant  marked  by  the  commencement  of  this  wave,  in  the  mauometric 
trace  inscribed  by  the  pressure  within  the  first  part  of  the  arch  of  the  aorta 
itself,  practically  marks  the  instant  of  closure  of  the  aortic  valve.  We  have 
seen  (p.  130)  that  this  doctrine  has  been  made  use  of  in  the  elucidation  of  the 
curve  of  the  pressure  within  the  ventricle. 

The  Diagnostic  Limitations  of  the  SphygmogTam. — The  feeling  of 
the  pulse,  imperfect  as  is  the  most  skilled  touch,  cannot  be  replaced  by  the 
use  of  the  sphygmograph.  The  presence,  between  the  cavity  of  the  artery 
and  the  surface  of  the  body,  of  a  quantity  of  tissue  the  amount  and  elasticity 
of  which  differ  in  different  people,  and  even  differ  over  neighboring  points  of 
the  same  artery,  renders  it  impossible  so  to  adjust  the  spring  of  the  sphygmo- 
graph as  to  be  able  to  obtain  a  reliable  base-line  corresponding  to  the  abscissa, 
or  line  of  atmospheric  pressure,  in  the  case  of  the  manometric  curve  of  blood- 
pressure.  The  effects  produced  by  slight  differences  in  the  placing  of  the 
instrument  tend  to  the  same  result.  By  the  absence  of  such  a  base-line  the 
sphygmographic  curve  is  shorn  of  quantitative  value  as  a  curve  of  blood- 
pressure,  and  cannot  give  information  as  to  whether,  in  clinical  language,  the 
pulse  be  hard  or  soft,  large  or  small.  Nor  can  a  long  or  short  pulse  be  iden- 
tified from  the  appearance  of  the  sphygmogram.1  The  pulse-trace  still 
requires  much  elucidation ;  but  when  further  study  shall  have  rendered 
clearer  the  true  extent,  the  normal  variations,  and  the  causes  of  the  complex 
and  incessant  oscillations  of  the  walls  of  the  arteries,  it  may  well  be  believed 
that  both  physiology  and  practical  medicine  will  have  gained  an  important 
insight  into  the  laws  of  the  circulation  of  the  blood. 

P.  The  Movement  of  the  Lymph. 

The  Lymphatic  System. — The  lymph  is  contained  within  the  so-called 
lymphatic  system,  the  nature  of  which  may  be  summarized  as  follows  : 

The  lymph  appears  first  in  innumerable  minute  irregular  gaps  in  the  tis- 
sues, which  gaps  communicate  in  various  ways  with  one  another,  and  with 
miuute  lymphatic  vessels,  which  latter,  when  traced  onward  from  their  begin- 
nings, presently  assume  a  structure  comparable  to  that  of  narrow  veins  with 
very  delicate  walls  and  extremely  numerous  valves.  These  valves  open  away 
from  the  gaps  of  the  tissues,  as  the  valves  of  the  veins  open  away  from  the 
capillaries.  The  lymphatic  vessels  unite  to  form  somewhat  larger  ones,  each 
of  which,  however,  is  of  small  calibre  as  compared  with  a  vein  of  medium 
size,  until  at  length  the  entire  system  of  vessels  ends,  by  numerous  openings, 
in  two  main  trunks  of  very  unequal  importance,  the  thoracic  duet  and  the 
right  lymphatic  duct.  The  latter  is  exceedingly  short,  and  receives  the  ter- 
minations of  the  lymphatics  of  a  very  limited  portion  of  the  body  ;  the  termi- 
nations of  all  the    rest,  including  the   lymphatics  of  the   alimentary  canal,  are 

1  M.  von  Frey  :   /'"'  Untersuehumg  des  Pulses,  1892,  8.  35. 
Vol.  I.— 10 


146  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

received  by  the  thoracic  duct,  which  runs  the  whole  length  of  the  chest. 
Both  of  the  main  ducts  have  walls  which,  relatively,  are  very  thin  ;  and,  like 
the  smaller  lymphatics,  the  ducts  are  abundantly  provided  with  valves  so 
disposed  as  to  prevent  any  regurgitation  of  lymph  from  either  duct  into  its 
branches.  Each  duct  terminates  on  one  side  of  the  root  of  the  neck,  where, 
in  man,  the  cavity  of  the  duet  joins  by  an  open  mouth  the  confluence  of  the 
internal  jugular  and  subclavian  veins  where  they  form  the  innominate  vein. 
At  the  opening  of  each  duet  into  the  vein  a  valve  exists,  which  permits  the 
free  entrance  of  lymph  into  the  vein,  but  forbids  the  entrance  of  blood  into 
the  duet. 

It  is  a  peculiarity  of  the  lymphatic  system  that  some  of  its  vessels  end  and 
begin  by  open  mouths  in  the  so-called  serous  cavities  of  the  body — those  vast 
irregular  interstices  between  organs  the  membranous  walls  of  which  interstices 
are  known  as  the  peritoneum,  the  pleura?,  and  the  like.  For  present  purposes, 
therefore,  these  serous  cavities  may  be  regarded  as  vast  local  expansions  of 
portions  of  the  lymph-path.  Another  peculiarity  of  the  lymphatic  system  de- 
pends upon  the  presence  of  the  lymphatic  glands  or  ganglia,  which  also  are 
intercalated  here  and  there  between  the  mouths  of  lymphatic  vessels  which 
enter  and  leave  them.  The  nature  and  importance  of  these  bodies  have  been 
referred  to  in  dealing  with  the  origin  of  the  leucocytes  and  the  nature  of  the 
lymph  (p.  47).  For  the  present  purposes  the  ganglia  are  of  interest  in  this, 
that  the  lymph  which  traverses  their  texture  meets,  in  so  doing,  with  much 
resistance  from  friction.  Physiologically,  therefore,  the  lymph-path  as  a  whole, 
extending  from  the  tissue-gaps  to  the  veins  at  the  root  of  the  neck,  both  differs 
from,  and  in  some  respects  resembles,  the  blood-path  from  the  capillaries  to  the 
same  point. 

The  origin  of  the  lymph  has  been  discussed  already  (p.  71),  and  has  been 
found  to  be  partly  from  the  blood  in  the  capillaries,  and  partly  from  the  tis- 
sues, to  say  nothing  of  the  products  directly  absorbed  from  the  alimentary 
canal  during  digestion.  The  quantity  of  material  which  leaves  the  lymph-path 
and  enters  the  blood  during  twenty-four  hours  is  undoubtedly  large,  amount- 
ing, in  the  dog,  to  about  sixty  cubic  centimeters  for  each  kilogram  of  body- 
weight.  The  movement  of  the  lymph  is,  therefore,  of  physiological  import- 
ance ;  and  the  causes  of  this  movement  must  now  be  considered. 

Differences  of  Pressure. — It  is  a  striking  fact  that  in  man  and  the 
other  mammals  there  exist  no  "  lymph-hearts"  for  the  maintenance  of  the 
lymphatic  How.  The  fundamental  causes  of  the  movement  of  the  lymph 
are  that  at  the  beginning  of  its  path  in  the  gaps  of  the  tissues  it  is  under 
considerable  pressure;  that  at  the  end  of  its  path  at  the  veins  of  the  neck 
it  is  under  very  low  pressure,  which  often,  if  not  usually,  is  negative;  and 
that  throughout  the  lymph-path  the  valves  are  so  numerous  as  to  work 
effectively  againsl  regurgitation.  The  pressure  of  the  lymph  in  the  gaps  of 
the  tissues  has  been  estimated  at  one  half,  or  more,  of  the  capillary  blood- 
pressure,]  which  latter  has  been  stated  (p.  84)  to  be  from  24  to  54  millimeters 

1  A.  Landerer:  Die  Qewebsspannung in  ihrem  Einfluss  auf  die  SrUieheBlut-  und  Lymphbewegung, 
Leipzig,  1884,  S.  103. 


CIRCULA  TION.  1 4  7 

of  mercury.  The  difference  between  one  half  of  either  of  these  pressures  and 
the  pressure  in  the  veins  of  the  neck,  which  pressure  i-  not  far  from  zero,  is 
quite  enough  to  produce  a  flow  from  the  one  point  to  the  other.  To  this  flow 
a  resistance  is  caused  by  the  friction  along  the  lymph-path,  which  resistance 
causes  the  lymph  to  accumulate  in  the  gaps  of  the  tissues,  and  the  pressure 
there  to  rise,  until  the  tension  of  the  tissues  resist>  further  accumulation  more 
forcibly  than  friction  resists  the  onward  movement  of  the  lymph.  The  little- 
known  forces  which  continually  produce  fresh  lymph,  and  pour  it  into  the 
tissue-gaps  against  resistance,  cannot  be  discussed  here  further  than  has  been 
done  in  treating  of  the  origin  of  the  lymph  (p.  71). 

Thoracic  Aspiration. — The  causes  have  already  been  stated  fully  of  that 
low,  perhaps  negative,  pressure  in  the  veins  at  the  root  of  the  neck  which  ren- 
ders possible  the  continuous  discharge  of  the  lymph  into  the  blood  (p.  95). 
It  need  only  be  noted  here  that  when  inspiration  rhythmically  produces,  or 
heightens,  the  suction  of  blood  into  the  chest,  it  must  also  produce,  or  heighten, 
the  suction  of  lymph  out  of  the  mouths  of  the  thoracic  and  right  lymphatic 
ducts.  Moreover,  as  the  thoracic  duct  lies  with  most  of  its  length  within  the 
chest,  each  expansion  of  the  chest  must  tend  to  expand  the  main  part  of  the 
duct,  and  thus  to  suck  into  it  lymph  from  the  numerous  lymphatics  which 
join  the  duct  from  without  the  chest ;  while  the  numerous  valves  in  the  duct 
must  promptly  check  any  tendency  to  regurgitation  from  the  neck. 

The  Bodily  Movements  and  the  Valves. — Like  the  flow  of  the  blood  in 
the  veins,  the  flow  of  the  lymph  in  its  vessels  is  powerfully  assisted  by  the 
pressure  exerted  upon  the  thin-walled  lymphatics  by  the  contractions  of  the 
skeletal  muscles;  for  the  very  numerous  valves  of  the  lymphatics  render  it 
impossible  for  the  lymph  to  be  pressed  along  them  by  this  means  in  any  other 
than  the  physiological  direction  toward  the  venous  system.  Experiment  show- 
that  even  passive  bending  and  straightening  of  a  limb  in  which  the  mus- 
cles remain  relaxed,  increases  to  a  very  great  extent  the  discharge  of  lymph 
from  a  divided  lymphatic  vessel  of  that  limb.  It  is  probable,  therefore, 
that  movement  in  any  external  or  internal  part  of  the  body,  however  pro- 
duced, tends  to  relieve  the  tension  in  the  tissues  by  pressing  the  Lymph  along 
its  path. 

Conclusion. — The  movement  of  the  lymph  produced  in  these  various  ways 
is  doubtless  irregular;  but  a  substance  in  solution,  injected  into  the  blood,  can 
be  identified  in  the  lymph  collected  from  an  opening  in  the  thoracic  dint  at 
the  neck  in  from  four  to  seven  minute-,  after  the  injection.1  The  physiological 
importance  of  the  Ivmph-movement  Is  shown  not  only  by  the  large  amount 
of  matter  which  daily  leaves  the  lymphatic  system  to  join  the  blood,  but  also 
by  the  evil  effects  which  result  from  an  undue  accumulation  of  lymph,  more 
or  less  changed  in  character, in  the  gaps  of  the  tissues.  Such  an  accumulation 
constitutes  dropsy.  It  may  occur  in  a  scroti-  cavity  or  in  the  subcutaneous 
tissue;  in  the  latter  case  giving  rise  to  a   peculiar  swelling  which  "pit-  on 

1  S.  Tschirwinsky  :  "Zur  Frage  iiber  'lie  Schnelligkeil  <!<•-  Lymphstromee  und  der  Lymph- 
filtration,"  Centralblatt  fur  Physioloiji' ,  L895,  Band  ix.  S.  49. 


148  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

pressure."     Any  tissue  the  meshes  of  which  are  thus  engorged  with  lymph  is 
said  tn  be  "  (edematous."1 


PART  II.— THE  INNERVATION  OF  THE  HEART.2 

It  has  long  been  known  thai  the  frog's  heart  can  be  kept  beating  for  many 
hours  after  its  removal  from  the  body.  In  1881,  Martin  succeeded  in  main- 
taining the  heat  of  the  dog's  heart  after  its  complete  isolation  from  the  central 
nervous  system  and  the  systemic  blood-vessels.  Ludwigand  his  pupils  have 
attained  the  same  result  in  a  different  way.  In  1895,  Langendorif  was  able 
by  circulating  warmed  oxygenated,  defibrinated  blood  through  the  coronary 
vessels  to  maintain  the  hearts  of  rabbits,  eats,  and  dogs  in  activity  after  their 
total  extirpation  from  the  body.  Even  pieces  removed  from  the  ventricle 
will  contract  for  hours  if  fed  with  blood  through  a  cannula  in  the  branch  of 
the  coronary  artery  which  supplies  them.3  It  is  evident,  therefore,  that  the 
cause  of  the  rhythmic  beat  of  the  heart  lies  within  the  heart  itself,  and  not 
within  the  central  nervous  system. 

Cause  of  Rhythmic  Beat. — It  has  been  much  disputed  whether  the  car- 
diac muscle  possesses  the  power  of  rhythmical  contraction  or  whether  the 
rhythmic  beat  is  due  to  the  periodic  stimulation  of  the  muscle  by  the  discharge 
of  nerve-impulses  from  the  ganglion-cells  of  the  heart.  The  arrangement  of 
the  ganglion-cells  and  nerves  suggests  the  latter  view. 

The  Intracardiac  Ganglion-cells  and  Nerves. — In  the  frog  the  cardiac  nerves 
arise  by  a  single  branch  from  each  vagus  trunk  and  run  along  the  great  veins 
through  the  wall  of  the  sinus  venosus,  where  many  ganglion-cells  are  found, 
to  the  auricular  septum.  Here  they  unite  in  a  strong  plexus  richly  provided 
with  ganglion-cells.  Two  nerves  of  unequal  length  and  thickness  leave  this 
plexus  and  pass  along  the  borders  of  the  septum  to  the  auriculo-ventricular 
junction,  where  each  enters  a  conspicuous  mass  of  cells  known  as  Bidder's 
ganglion.  Ventricular  nerves  spring  from  these  ganglia  and  can  be  followed 
with  the  unaided  eye  some  distance  on  the  ventricle.  With  the  chloride-of- 
gold  method,  the  methylene-blue  stain,  and  especially  the  nitrate-of-silver  im- 
pregnation, the  ventricular  nerves  can  be  traced  to  their  termination.  Some 
difference  of  opinion  exists  regarding  the  manner  of  their  distribution  and  the 
precise  nature  of  their  terminal  organs.  The  following  facts,  however,  may  be 
considered  established  both  for  the  batrachian  and  the  mammalian  heart.4 

The    ventricular  nerves  form  a  rich   plexus  beneath  the  pericardium  and 

1  From  ol6qfin}  a  swelling. 

"The  literature  of  the  innervation  of  the  heart  and  blood-vessels  is  now  bo  large  that  only 
references  to  some  of  the  principal  investigations  published  since  1892  can  be  given  here.  For 
the  titles  of  works  prior  t<>  thai  date,  the  reader  may  consult  Tigerstedt's  Lehrbueh  der  Physiolo- 
gic des  Kreislaufes,  1S93. 

3  Porter:  Journal  <>)   Experimented  Medicine,  1897,  ii.  p.  391. 

'The  literature  of  this  subject  has  been  collected  by  Heymansand  Demoor:  Archives  (Beige) 
./.   Biologie,  1895,  xiii.  j>.  619. 


CIR  CULA  TION.  1 49 

endocardium.  Branches  from  these  plexuses  form  :i  third  plexus  in  the  myo- 
cardium or  heart  muscle,  from  which  arise  a  vast  number  of  non-medullated 
terminal  nerves,  enveloping  the  muscle-fibres  and  ending  in  small  enlargements 
or  nodosities  of  various  forms.  Similar  ,%  varicose  "  enlargements  are  observed 
along  the  course  of  the  nerves.  The  nerve-endings  are  in  contact  with  the 
naked  muscle-substance,  the  mode  of  termination  resembling  in  general  that 
observed  in  non-striated  muscle.  Ganglion-cells  are  found  chiefly  in  the 
auricular  septum  and  the  auriculo-ventricular  furrow,  but  arc  present  also 
beneath  the  pericardium  of  the  upper  half  of  the  ventricle.  Xo  ganglia  have 
as  yet  been  satisfactorily  demonstrated  within  the  apical  half  of  the  ventricle,1 
and  most  observers  do  not  admit  their  presence  within  the  ventricular  muscle 
itself.      The  nerve-cells  are  unipolar,  bipolar,  or  multipolar. 

Certain  unipolar  cells  in  the  frog  are  distinguished  by  a  spherical  form,  a 
pericellular  network,  and  two  processes — namely,  the  axis-cylinder  or  straight 
process,  and  the  spiral  process.  The  latter  is  wound  in  spiral  fashion  about 
the  axis-cylinder,  ending  in  the  pericellular  net.  According  to  Retzius  and 
others,  the  spiral  is  not  really  a  process  of  the  cell,  but  arises  in  a  distant  extra- 
cardiac  cell  and  carries  to  the  heart-cell  a  nervous  impulse  which  is  transmitted 
from  the  spiral  process  to  the  cell  by  means  of  the  contact  between  the  peri- 
cellular net  and  the  cell-body.  Section  of  the  cardiac  fibres  of  the  vagus 
causes  the  spiral  "  process  "  and  pericellular  net  to  degenerate,  the  cell-body 
and  axis-cylinder  process  remaining  untouched,  showing  that  the  spiral  process 
is  the  terminal  of  a  nerve-fibre  running  in  the  vagus  trunk.2 

Nerve-theory  of  Heart-beat. — The  theory  of  the  nervous  origin  of  the 
heart-beat  rests  in  part  on  the  correspondence  between  the  degree  of  contrac- 
tility of  the  various  parts  of  the  heart  and  the  number  of  nerve-cells  present 
in  them.  Thus  the  power  of  rhythmical  contraction  is  greater  in  the  auricle, 
in  which  there  are  many  cells,  than  in  the  ventricle,  in  which  there  are  fewer. 
The  properties  of  the  apical  half,  or  "apex,"  of  the  ventricle  are  considered 
to  be  of  especial  importance  in  the  study  of  this  problem,  because  the  apex,  as 
has  been  said,  is  believed  to  contain  no  ganglion-cells.  This  part  of  the  ven- 
tricle stops  beating  when  separated  from  the  heart,  while  the  auricles  and  the 
ventricular  stump  continue  to  beat.  The  apex  need  not  be  cut  away  in  order 
to  isolate  it.  By  ligating  or  squeezing  the  frog's  ventricle  across  the  middle 
with  a  pair  of  forceps  the  tissues  at  the  junction  of  the  upper  and  the  lower 
half  of  the  ventricle  can  be  crushed  to  the  point  at  which  physiological  con- 
nection is  destroyed  but  physical  continuity  still  preserved.  Such  frogs  have 
been  kept  alive  as  long  as  six  weeks.  The  apex  does  not  as  a  rule  beat  again. 
The  exceptions  can  be  explained  as  the  consequence  of  accidental  stimulation. 
The  conclusion  drawn  Is  that  the  apex,  in  which  ganglion-cells  have  not  been 
satisfactorily  demonstrated,  has  not  the  power  of  spontaneous  pulsation  which 

'Schwartz:  Archiv  fur  mikroskopiache  Anatomie,  1899,  liii.  S.  63.  Compare  Dogiel  :  Ibid., 
S.  237. 

2Nikolajew:  Archiv  fur  Physiologie,  1893,  Suppl.  Bd.,  S.  7.".. 


150  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

distinguishes  the  remainder  of  the  heart.  This  view  is  further  supported  by 
the  observation  thai  a  slight  stimulus  applied  to  the  base  of  a  resting  ventricle 
will  often  provoke  a  series  of  contractions,  while  the  same  stimulus  applied  to 
th«'  apex  will  cause  but  ;i  single  contraction. 

Much  may  be  hoped  from  comparative  studies.  In  the  medusas,  for  ex- 
ample, the  margin  of  the  swimming  bell,  by  the  rhythmical  contraction  of 
which  the  animal  is  driven  through  the  water,  is  provided  with  a  double 
nerve-ring  and  ganglion-cells,  while  the  centre  contains  only  scattered  and 
infrequent  ganglion-cells.  \i'  the  margin  is  separated  from  the  centre  and 
both  arc  placed  in  sea-water,  only  the  pari  containing  many  nerve-cells  beats 
rhythmically.  Loeb  concludes  that  inasmuch  as  the  whole  medusa  (Gonione- 
iiiiis)  beats  in  sea-water  in  the  rhythm  of  the  margin,  the  failure  of  the  iso- 
lated centre  to  beat  in  that  medium  can  only  be  explained  by  the  lack  of 
nerve-cells.1 

The  fact  that  the  normal  contraction  begins  in  the  sinus,  Howell  explains 
by  the  greater  sensitiveness  of  that  part  to  chemical  stimulation.2 

The  action  of  muscarin  on  the  heart  is  often  held  to  indicate  the  nervous 
origin  of  the  heart-beat.  Muscarin  arrests  the  heart  of  the  frog  and  other 
vertebrates,  but  has  no  similar  action  on  any  other  muscle  either  striped  or 
smooth,  nor  does  it  arrest  the  heart  of  insects  and  mollusks.  It  follows  that 
muscarin  does  not  cause  arrest  by  acting  directly  upon  the  contractile  material 
of  the  heart.  The  contractile  material  being  excluded,  the  assumption  of  a 
nervous  mechanism  on  the  integrity  of  which  the  heart-beat  depends  seems 
necessary  to  explain  the  effect  of  the  poison. 

Further  arguments  are  based  on  uncertain  analogies  between  the  heart  and 
other  rhythmically  contracting  organs. 

Muscular  Theory  of  Heart-beat? — The  evidence  just  stated  cannot  be  re- 
garded  as  proof  of  the  nervous  origin  of  the  heart-beat.  The  most  that  can 
be  claimed  is  that  it  makes  such  a  conception  plausible.  The  cause  of  the 
beat  probably  lies  in  the  contractile  substance  rather  than  the  nerve-cells. 
It  is.  at  all  events,  certain  that  the  cardiac  muscle  is  capable  of  prolonged 
rhythmic  contraction.  It  has  been  shown  that  a  strip  of  muscle  cut  from  the 
apex  of  the  tortoise  ventricle  and  suspended  in  a  moist  chamber  begins  in  a 
few  hours  to  beat  apparently  of  its  own  accord  with  a  regular  but  slow 
rhythm,  which  has  been  seen  to  continue  as  long  as  thirty  hours.  If  the  strip 
i-  cut  into  pieces  and  placed  on  moistened  glass  slides,  each  piece  will  contract 
rhythmically.      Vet  in  the  apex  of  the  heart  no  nerve-cells  have  been  found. 

The  apex  of  the  batrachian  heart  will  beat  rhythmically  in  response  to  a 
constant  stimulus.  Thus  if  the  apex  is  suspended  in  normal  saline  solution 
and  a  constant  electrical  current  kept  passing  through  it,  beats  will  appear 
after  a  time,  the  frequency  of  pulsation  increasing  with  the  strength  of  the 

1  Loeb:  American  Journal  of  Physiology,  L900,  iii.  p.  383. 
» Howell:    Ibid.,  ii.  p.  47. 

3  A  valuable  bibliography  is  given  by  Engelmann:  Archiv  fur  die  gesammte  Physiologic, 
1896,  lxv.  p.  lO'.t;  see  also  Ibid.,  p.  035. 


CIRCULATION.  151 

current.1  Very  strong  currents  cause  tonic  contraction.  An  apex  made  inac- 
tive by  Bernstein's  crushing  can  be  made  to  beat  again  by  clamping  the  aorta 
and  thus  raising  the  endocardiac  pressure.  Chemical  stimulation  is  also  effec- 
tive. Delphinin,  quinine,  muscarin  with  atropin,  atropin  alone,  morphin 
and  various  other  alkaloids,  dilute  mineral  acids,  dilute  alkalies,  bile,  sodium 
chloride,  alcohol,  and  other  bodies,2  when  painted  on  the  resting  ventricle,  call 
forth  a  longer  or  shorter  series  of  beats.  Stimulation  with  induction  shocks 
gives  a  similar  result. 

Other  muscles  in  which  no  nerve-cells  have  been  discovered  can  contract 
rhythmically.  Thus  the  bulbus  aortse  of  the  frog  beats  regularly  after  its 
removal  from  the  body,  even  the  smallest  pieces  showing  under  the  microscope 
rhythmical  contractions.  Engelmann,  who  observed  this  fact,  declares  that 
the  entire  bulbus  is  lacking  in  nerve-cells.  This  is  contradicted  by  Dogiel ; 
yet  it  seems  hardly  reasonable  that  these  "  smallest  pieces  "  which  Engelmann 
mentions  were  each  provided  with  ganglion-cells.  It  is  more  probable  that  the 
contractions  were  the  result  of  a  constant  artificial  stimulus.  Curarized  stri- 
ated muscles  placed  in  certain  saline  solutions  may  contract  from  time  to  time. 
The  hearts  of  many  invertebrates  in  which  ganglion-cells  are  apparently  absent 
beat  rhythmically. 

Much  has  been  made  of  the  fact  that  the  ganglion-cells  grow  into  the  heart 
long  after  the  cardiac  rhythm  is  established,  showing  that  the  embryonic  heart 
muscle  has  rhythmic  contractile  powers.  The  adult  heart  muscle,  it  is  alleged, 
retains  certain  embryonic  peculiarities  of  structure,  and  as  structure  and  func- 
tion are  correlated,  should  also  retain  the  embryonic  power  of  contraction 
without  nerve-cells. 

A  positive  demonstration  that  the  nerve-cells  in  the  heart  are  not  essential 
to  its  contractions  is  secured  by  removing  the  tip  of  the  ventricle  of  the  dog's 
heart  and  supplying  it  with  warm  defibrinated  blood  through  a  cannula  tied 
into  its  nutrient  artery.  Long-continued,  rhythmical,  spontaneous  contrac- 
tions are  thus  obtained.3  As  the  part  removed  contains  no  nerve-cells,  the 
observed  contractions  can  only  arise  in  the  muscular  tissue,  provided  we  make 
the  (at  present)  safe  assumption  that  the  nerve-fibres  d<>  not  originate  im- 
pulses capable  of  inducing  rhythmic  muscular  contractions.  The  demonstra- 
tion that  the  nerve-cells  are  not  essential  to  contraction,  places  us  one  step 
nearer  the  true  cause  of  contraction.  It  is  some  agency  acting  on  the  con- 
tractile substance.  Evidence  is  accumulating  that  this  agent  is  a  chemical 
substance,  or  substances,  brought  to  the  contractile  matter  by  the  blood. 
For  this  chemical  stimulation  calcium  is  apparently  essential,  and  for  rhythmic 
contraction  and   relaxation    Howell4  finds  a  certain    proportion  of  potassium 

1  Langendorff:  Archivfur  die  gesammte  Physiologic,  L895,  Ixi.  p.  33(5. 

2  Kaiser:  Zeitschnfi  fur  Biologic,  L895,  xxxii.  p.  (>. 

3  Porter:  Journal  of  Experimental  Medicine,  1X97,  ii.  p.  391. 

*  Howell :  American  Journal  of  Physiology,  1898,  ii.  p.  17;  Loeb:  Ibid.,  1900,  iii.  p.  394. 
The  reader  is  recommended  to  examine  these  BUggestive  papers  for  himself. 


152  AN  AMERICAN    TENT-BOOK    OF  PHYSIOLOGY. 

also  accessary.  Sodium  chloride  must  bo  present  to  preserve  the  osmotic 
equilibrium  between  contractile  tissue  and  surrounding  liquid.     As  phrased 

by  Loci),  it  may  be  assumed  that  the  sodium,  calcium,  and  potassium  ions 
must  exist  in  definite  proportions  in  the  tissue  which  is  expected  to  show 
rhythmical  activity.  Only  so  long  as  these  proportions  are  preserved  does 
the  tissue  possess  such  physical  properties  and  such  labile  equilibrium  as  to 
be  capable  of  rhythmical  processes  or  contractions. 

The  Excitation-wave. — The  change  in  form  which  constitutes  what  com- 
monly is  called  the  cardiac  contraction  is  preceded  by  a  change  in  electrical 
potential,  supposed  to  be  a  manifestation  of  the  unknown  process  by  which  the 
heart-muscle  is  excited  to  contract.  Both  the  contraction  and  the  electrical 
change  sweep  over  the  heart  in  the  form  of  waves,  and  it  has  become  the  cus- 
tom to  speak  of  the  electrical  change  as  the  excitation-wave.  It  should  not  be 
forgotten,  however,  that  this  usage  rests  merely  on  an  assumption,  for  the  real 
nature  of  the  excitation  is  still  a  mystery.  The  contraction-wave  begins  nor- 
mally at  the  great  veins,  travels  rapidly  through  the  auricle,  and,  after  a  dis- 
tinct interval,  spreads  through  the  ventricle.  The  excitation-wave,  which  pre- 
cedes and  is  the  cause  of  the  contraction,  probably  takes  the  same  course,1  and 
in  fact  it  is  possible  to  show  that  the  change  in  electrical  potential  actually 
begins  under  normal  conditions  at  the  great  veins  and  passes  thence  over  the 
entire  heart.  But  this  sequence  is  not  invariable.  The  ventricle  under  abnor- 
mal conditions  has  been  seen  to  contract  before  the  auricle,  the  normal  sequence 
of  great  veins,  auricle,  and  ventricle  being  reversed.2  The  energy  of  the  ven- 
tricular muscle-cell  may,  therefore,  be  discharged  by  an  excitation  arising 
within  the  ventricle  itself.  Evidence  of  this  is  afforded  also  by  the  experi- 
ment of  Wooldridge,  who  isolated  the  ventricles  by  drawing  a  silk  ligature 
tightly  about  the  auricles  at  their  junction  with  the  ventricles,  completely 
crushing  the  muscle  and  nerves  of  the  auricle  in  the  track  of  the  ligature  with- 
out tearing  through  the  more  resistant  pericardium.  This  experiment  was 
repeated  the  following  year  by  Tigerstedt,  who  devised  a  special  clamp  for 
crushiug  the  auricular  tissues.  Both  observers  found  that  the  auricles  and 
ventricles  continued  to  beat.  The  rhythm,  however,  was  no  longer  the 
same.  The  ventricular  beat  was  slower  than  before  and  was  independent  of 
the  brat  of  the  auricle.  Thus  the  ventricle,  no  longer  connected  physiologically 
with  the  auricle,  develops  a  rhythm  of  its  own,  an  idio-ventricular  rhythm.  It 
seems  improbable  that  the  very  small  part  of  the  auricular  tissue  which  cannot 
be  included  in  Wooldridge's  ligature  for  fear  of  closing  the  coronary  arteries 
should  be  able  to  maintain  the  ventricular  contractions. 

Independent  contraction  is  said  to  be  secured  by  properly  regulated  excita- 
tion of  the  cardiac  end  of  the  cut  vagus  nerve.  Stimuli  of  one  second  duration 
applied  to  the  vagus  at  intervals  of  six  to  seven  seconds  arrest  the  auricles 
completely,  but  do  not  stop  the  ventricles,  except  during  the  second  of  stimu- 
lation.    The  ventricles,  now  dissociated  from  the  auricles,  beat  with  a  rhythm 

1  Bottazzi :  Lo  sperimentale,  1 898,  li.  No.  2. 

1  Recently  studied  by  En^elmann  :  An hiv  fur  die  gesammte  Physiologic,  1895,  lxi.  p.  275. 


CIRCULATION. 


153 


different  from  that  which  characterized  the  normal  heart.  The  force  of  this 
demonstration  is  somewhat  weakened  by  the  possibility  that  the  auricles, 
although  not  beating  themselves,  might  still  excite  the  ventricles  to  contraction. 
Conduction  of  the  Excitation. — If  the  points  of  non-polarizable  electrodes 
are  placed  on  the  surface  of  the  ventricle  and  connected  with  a  delicate  galvan- 
ometer, a  variation  of  the  galvanometer  needle  will  be  seen  with  each  ventric- 
ular beat.  If  one  electrode  is  placed  near  the  base  of  the  heart  and  the  other 
near  the  apex  it  is  seen  that  the  former  electrode  becomes  negative  before  the 
latter,  indicating  that  the  part  of  the  heart  muscle  on  which  the  basal  electrode 
rests  is  stimulated  before  the  apical  portion,  and  that  the  difference  in  electrical 
potential,  or  excitation-wave,  according  to  the  prevailing  hypothesis,  travels  as 
a  wave  over  the  ventricle  from  the  base  to  the  apex  (see  Fig.  27).  Burdon- 
Sanderson  and  Page  have  found  that  the  duration  of  the  difference  of  poten- 
tial is  about  two  seconds  in  the  frog's  heart  at  ordinary  temperatures.  Cooling 
lengthens  the  period  of  negativity,  warming  diminishes  it.  Some  observers 
believe  that  the  excitation-wave  under  certain  conditions  returns  toward  the 
base  after  having  reached  the  apex.  The  speed  of  the  excitation-wave  has  been 
measured  by  the  interval  between  the  appearance  of  negative  variation  in  the 
ventricle  when  the  auricle  is  stimulated  first  near  and  then  as  far  as  possible 


Fig.  27.— The  electrical  variation  in  the  spontaneously  contracting  heart  of  the  frog,  recorded  by  a 
capillary  electrometer,  the  apex  being  connected  with  the  sulphuric  acid  ami  the  base  with  the  mercury 
of  the  electrometer.  The  changes  in  electrical  potential  are  shown  by  the  line  e,  > ,  which  is  obtained  by 
throwing  the  shadow  of  the  mercury  in  the  capillary  <>n  a  travelling  sheet  of  sensitized  paper.  The  con 
traction  of  the  heart  is  recorded  by  the  line  h,  h  :  time,  in  „',,  second,  by  I.  t.  The  curves  read  from  hit 
P.  right.  The  electrical  variation  is  diphasic;  in  the  first  phase  the  base  is  negative  to  the  apex  ;  in  the 
second,  the  apex  is  negative  to  the  base;  the  negative  variation  passes  as  a  wave  from  base  to  apex 
(Waller,  1887,  p.  231). 

from  the  non-polarizable  electrodes.  The  interval  is  the  time  which  the  excita- 
tion-wave requires  to  pass  the  distance  between  the  two  points  stimulated.  The 
average  rate  is  at  least  50  millimeters  per  second.1  The  negative  variation 
begins  apparently  instantly  ai'ter  the  application  of  the  stimulus.  Its  phases 
and  their  characteristics  have  been  described  by  Engelmann. 
The  latent  period  of  a  frog's  heart  muscle  is  about  0.08  second. 

1  Burdon-Sanderson  and  Page  (Journal  of  Physiology,  1880,  ii.  j>.  4Jti  i  give  125  millimeters 

per  second. 


154  AX  AMERICAN   TEXT-BOOK    OE   PHYSIOEOGY. 

Although  the  normal  course  of  the  excitation-wave  is  from  base  to  apex,  it 
can  be  made  to  travel  in  any  direction.  If  the  frog's  ventricle  is  cut  with  fine 
scissors  into  a  number  of  pieces  in  such  a  way  as  to  leave  small  bridges  of 
heart-tissue  between  each  piece,  and  any  one  of  the  pieces  is  stimulated,  the 
contraction  will  begin  in  the  stimulated  piece  and  then  run  from  piece  to  piece 
over  the  connecting  bridges  until  all  have  successively  contracted.  The  direc- 
tion in  which  the  excitation-wave  travels  can  thus  be  altered  at  the  pleasure 
of  the  operator. 

Whether  the  excitation  is  propagated  from  mnscle-cell  to  muscle-cell  or  by 
means  of  nerve-fibres  has  given  rise  to  much  discussion.  Anatomical  evidence 
can  be  adduced  on  both  sides.  On  the  one  hand  the  rich  plexus  of  nerve- 
fibres  everywhere  present  in  the  heart-muscle  suggests  conduction  through 
nerves  ;  on  the  other  is  the  intimate  contact  of  neighboring  muscle-cells  over 
a  part  at  least  of  their  surface,  thus  bringing  one  mass  of  irritable  protoplasm 
against  another  and  offering  a  path  by  which  the  excitation  might  travel  from 
cell  to  cell. 

If  the  excitation-wave  were  conducted  by  means  of  nerves,  the  difference 
between  the  moment  of  contraction  of  the  ventricle  when  the  auricle  is  stimu- 
lated near  the  ventricle,  and  again  as  far  as  possible  from  the  ventricle,  should 
be  very  slight,  because  of  the  great  speed  at  which  the  nervous  impulse  travels 
(about  33  meters  per  second).  If,  on  the  contrary,  the  conduction  were  by 
means  of  muscle,  the  difference  would  be  relatively  much  greater,  correspond- 
ing to  the  much  slower  conductivity  of  muscular  tissue.  It  has  been  found  by 
Engelmann  that  the  ventricle  contracts  later  when  the  auricle  is  stimulated  far 
from  the  ventricle  than  when  it  is  stimulated  near  the  ventricle.  The  rate  of 
propagation  being  calculated  from  the  difference  in  the  time  of  ventricular  con- 
traction was  found  to  be  90  millimeters  per  second,  which  is  about  300  times 
less  than  the  rate  which  would  have  been  obtained  had  conduction  over  the 
measured  distance  taken  place  through  nerves.1  Hence  the  stimulus  that  trav- 
els through  the  auricle  to  the  ventricle  and  causes  its  contraction  should  be 
propagated  in  the  auricle  by  muscle-fibres  and  not  by  nerves. 

It  is  possible  to  cut  the  ventricular  muscle  in  a  zigzag  or  spiral  fashion 
that  makes  probable  the  severance  of  all  the  nerve-fibres  in  the  line  of  the 
cut,  and  yet  the  contraction  will  pass  from  one  end  to  the  other  of  the  isolated 
strip.2 

Passage  of  Excitation-wave  from  Auricle  to    Ventricle. — The  normal  con- ' 
traction  of  the  heart  begins,  as  has  been  said,  at  the  junction  of  the  great 
veins  and   the  auricle,  spreads  rapidly  over  the  auricle  and,  after  a  distinct 
pause,  reaches  the  ventricle.     The  normal  excitation-wave  preceding  the  con- 
traction passes  likewise  from  the  auricle  to  the  ventricle  and  is  delayed  at  or 

1  Engelmann  :  Archivfiir  die  gesammte  Physiologie,  1896,  lxii.  p.  549. 

2  I'urter:  American  Journal  of  Physiology,  1899,  ii.  p.  127.  The  co-ordination  of  the  ven- 
tricles is  discussed  in  this  paper,  and  also  by  von  Vintschgau :  Archiv  fur  die  gesammte  Physi- 
ologie, 1899,  lxxvi.  p.  59. 


CIR  CULA  TION.  1 55 

near  the  auricula- ventricular  junction.  The  controversy  over  the  nervous  or 
muscular  conduction  of  the  excitation  within  the  auricle  and  ventricle  has 
been  extended  to  its  passage  from  auricle  to  ventricle.  A  path  for  conduction 
by  nerves  is  presented  by  the  numerous  nerves  which  go  from  the  auricle  to 
the  ventricle.  It  has  been  shown  recently  that  muscular  connections  also 
exist.  In  the  frog,  muscle-bundles  pass  from  the  auricle  to  the  ventricle 
where  the  auricular  septum  adjoins  the  base  of  the  ventricle.  Muscular 
bridges  pass  also  from  the  sinus  venosus  to  the  auricles  and  from  the  ventricle 
to  the  bulbus  arteriosus.1  These  muscle-fibres  appear  to  be  in  intimate  con- 
tact with  the  muscle-cells  of  the  divisions  of  the  heart  which  they  unite.  Gas- 
kell  believes  that  the  connecting  fibres  are  morphologically  and  physiologically 
related  to  embryonic  muscle,  and  therefore  possess  the  power  of  contracting 
rhythmically. 

The  delay  experienced  by  the  excitation  in  its  passage  from  the  auricle  to 
the  ventricle — in  other  words,  the  normal  interval  between  the  contraction  of 
the  auricle  and  the  contraction  of  the  ventricle — is  explained  by  those  favoring 
the  nervous  conduction  as  the  delay  which  the  excitation  experiences  in  dis- 
charging the  ganglion-cells  of  the  ventricle,  in  accordance  with  the  well-known 
hypotheses  of  the  retardation  of  the  nerve-impulse  in  sympathetic  ganglia 
and  the  slow  passage  of  the  nervous  impulse  through  spinal  cells. 

The  explanation  given  by  those  who  believe  in  muscular  conduction  is  that 
the  small  number  of  muscular  fibres  composing  the  bridge  between  auricle 
and  ventricle  acts  as  a  "  block  "  to  the  excitation-wave.  If  the  auricle  of  the 
tortoise  heart  is  cut  into  two  pieces  connected  by  a  small  bridge  of  auricular 
tissue,  the  stimulation  of  one  piece  will  be  followed  immediately  by  the  con- 
traction of  that  piece,  and  after  an  interval  by  the  contraction  of  the  other. 
The  smaller  the  bridge,  the  longer  the  interval ;  that  is  the  longer  the  excita- 
tion-wave will  be  in  passing  from  one  piece  to  another. 

The  duration  of  the  pause  or  "  block  "  in  the  frog  has  been  found  to  be  from 
0.15  to  0.30  second.  The  length  of  the  muscle-fibres  connecting  auricle  and 
ventricle  is  about  one  millimeter.  The  speed  of  the  excitation-wave  in  em- 
bryonic heart  muscle  is  from  3.6  to  11.5  millimeters  per  second.  The  duration 
of  the  pause  agrees,  therefore,  with  the  time  which  would  be  required  for 
muscular  conduction.2 

The  extensive  extirpations  of  the  auricular  nerves  which  have  been  made 
without  stopping  conduction  from  auricle  to  ventricle8 — for  example,  the  ex- 
tirpation of  the  entire  auricular  septum  of  the  frog's  heart — are  of  little 
importance  to  this  question,  since  the  great  number  of  aerve-cells  revealed  by 
recent  methods  make  it  improbable  that  any  extirpation  short  of  total  removal 
of  both  auricles  could  cut  off  all  the  nerve-cells  of  the  auricle. 

It   is  possible  to  explain  the  occurrence  of  intermittent  or  irregular  eon- 

1  Engelmann:  Archiv  fur  die  geaammUe  Physiologic,  1894,  lvi.  j>.  158. 
'  Engelmann  :   Tbid.,  p.  159. 
•Hofinann:  Ibid.,  L895,  lx.  j>.  169. 


156  AN    AMERICAN   TEXT-BOOK    OF   PHYSIOLOGY. 

tractions  by  alterations  in  the  conductivity  or  irritability  of  the  several  parts 
of  the  heart  successively  traversed  by  the  excitation  wave.  For  example, 
a  Lessening  of  the  normal  conductivity  at  the  auriculo-ventricular  junction 
might  permit  only  every  second  sino-auricular  impulse  to  reach  the  ventricle; 
in  this  ease  the  ventricle  would  drop  every  second  beat.  The  same  inter- 
mittence  would  result  if  the  irritability  ol*  the  ventricle  were  so  far  reduced 
that  it  could  not  respond  to  the  normal  excitation.1  Engelmann  has  recently 
found  that  ventricular  systole  lowers  the  conductivity  of  the  ventricle  for  a 
time.2 

Refractory  Period  and  Compensatory  Pause. — Schiff  found  in  1850 
that  the  heart  which  contracted  to  each  stimulus  of  a  series  of  slowly  repeated 
mechanical  stimuli  would  not  contract  to  the  same  stimuli  if  they  followed  each 
other  in  too  rapid  succession.  Kronecker  got  a  similar  result  with  induction 
shucks.  The  heart  contracted  to  every  stimulus  only  when  the  interval  between 
them  was  not  too  brief.  The  following  year  Marey  published  a  systematic 
study  of  the  phenomenon.  He  observed  that  the  irritability  of  the  heart  sank 
during  a  part  of  the  systole,  but  returned  during  the  remainder  of  the  systole 
and  the  following  diastole.  The  stimulus  which  fell  between  the  beginning  of 
the  systole  and  its  maximum  produced  no  extra  contraction,  whilst  that  which 
fell  between  the  maximum  of  one  systole  and  the  beginning  of  the  next 
called  forth  an  extra  contraction.  During  a  part  of  the  cardiac  cycle  therefore 
the  heart  is  "  refractory "  toward  stimuli.  The  irritability  of  the  heart  is 
removed  for  a  time  by  an  adequate  stimulus. 

Kronecker  and  Marey  noticed  further  that  stimulation  with  the  induction 
shock  during  the  non-refractory  period  did  not  influence  the  total  number  of 
systoles.  The  extra  systole  called  forth  by  the  artificial  stimulus  was  followed 
by  a  pause  the  length  of  which  was  that  of  the  normal  pause  plus  the  interval 
between  the  appearance  of  the  extra  systole  and  what  would  have  been  the  end 
of  the  cardiac  cycle  in  which  the  extra  systole  fell.  The  extra  length  of  this 
pause  restored  the  normal  frequency  or  rhythm.  It  was  called  the  compensa- 
tory pause  (see  Fig.  28).3 

The  systole  following  the  extra  contraction  and  its  compensatory  pause  is 
of  marked  strength,  at  least  in  the  surviving  mammalian  heart  (cat).  The 
weaker  the  extra  systole  the  stronger  the  first  subsequent  contraction. 
The  unusual  force  of  this  "compensatory  systole"  may  serve  to  compensate 
the  loss  in  the  output  of  the  heart  incident  to  the  disturbance  in  its  rhthym.4 

If  the  heart,  or  the  isolated  apex,  is  beating  at  a  rate  so  slow  that  an  extra 
contraction  falling  in  the  interval  between  two  normal  contractions  has  time  to 
complete  its  entire  phase  before  the  next  normal  contraction  is  due,  there  will 
be  no  compensatory  pause.5 

1Oehrwall:  Skandinavisches  Archiv fiir  Physiologie,  1898,  viii.  p.  1. 
2  Engelmann:   Archiv  fur  <U>  geswnmte  Plu/xiologie,  1896,  Ixii.  p.  543. 
'  (  lourtade:  Archives  de  Physioloffie,  1897,  p.  69. 

*  Langendurfl":   Archiv  fiir  >li>  gr.mminti'  f'ln/siolagie,  1898,  lxx.  p.  473. 
5  Kaiser:   Zeituclirifl  fiir  Biologic,  1895,  xxxii.  p.  449. 


CIRCULA  TIOX.  1 57 

The  refractory  phase  disappears  with  sufficiently  strong  stimuli,  especially 
if  the  heart  is  warmed.  In  such  a  case  an  artificial  stimulus  falling  in  the 
beginning  of  a  spontaneous  contraction  produces  an  extra  contraction.  This 
extra  contraction,  however,  comes  first  after  the  end  of  the  systole  during  which 
the  artificial  stimulation   is  made,  occurring  in   fact   toward   the  end  of  the 


Fig.  28. — The  refractory  period  and  compensatory  pause.  The  curves  are  recorded  by  a  writing  lever 
resting  on  the  ventricle  of  the  frog's  heart.  They  read  from  left  to  right.  A  break  in  the  horizontal  line 
below  each  curve  indicates  the  moment  at  which  an  induction  shock  was  sent  through  the  ventricle.  In 
curves  1,  2,  and  :;  the  ventricle  proved  refractory  to  this  stimulus;  in  the  remaining  curves,  the  stimulus 
having  fallen  outside  t.he  refractory  period,  an  extra  contraction  and  compensatory  pause  are  seen. 
Many  of  the  phenomena  mentioned  in  the  text  are  illustrated  by  this  figure  (Marey,  1876,  p.  72 

following  diastole.  The  latent  period  of  such  a  contraction  Lengthens  with 
the  length  of  the  interval  between  the  artificial  stimulation  and  the  end  of  the 
systole. 

A  refractory  period  has  been  demonstrated  in  the  auricle  of  the  frog1 
and  dog;2  in  the  ventricle  of  the  cat,  rabbit,  and  dog,  and  in  the  sinus 
venosus  and  bulbus  arteriosusof  the  frog,  h  is  said  noi  to  be  present  in 
the  lobster.3 

1  Engelmann:  Archiv  fitr  die  gescmmU  Physiologic,  1894,  li\.  p.  322. 

'Meyer:  Archives  de  Physiologic,  1893,  p.  185;  Cushny  and  .Matthews:  Journal  of  Physiology, 
1897,  xxi.  p.  213. 

8  Hunt,  Bookman,  and  Tierney  :  Centrcdblatt fur  Physiologic,  1897,  \i.  p.  276. 


158  AN    AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

In  some  cases,  the  extra  stimulus  provokes  not  merely  one,  but  two  or  three 
extra  contractions. 

The  amplitude  of  the  extra  contraction  increases  with  the  length  of  the 
interval  between  the  maximum  of  contraction  and  the  extra  stimulus.  If  the 
extra  stimulus  is  given  at  the  beginning  of  relaxation,  the  extra  contraction  is 
exceedingly  small ;  on  the  other  hand,  the  extra  contraction  may  be  greater 
than  the  primary  one,  when  the  stimulus  falls  in  the  pause  between  two  normal 
beats. 

The  supplementary  systole  of  the  auricle  is  sometimes  followed  by  a  sup- 
plementary systole  and  compensatory  pause  of  the  ventricle,  sometimes  by  the 
compensatory  pause  alone,  probably  because  the  excitation  wave  reaches  the 
ventricle  during  its  refractory  period.  Multiple  extra  contractions  of  the 
auricle  are  often  followed  by  the  same  number  of  extra  contractions  of  the 
ventricle.  If  the  frog's  heart  is  made  to  beat  in  reversed  order,  ventricle 
first,  auricle  second,  extra  contractions  of  the  ventricle  may  be  produced,  and 
will  cause  extra  contractions  of  the  auricle  with  compensatory  pause.  If  the 
reversed  excitation  wave  travelling  from  the  ventricle  to  the  auricle  reaches 
the  latter  during  auricular  systole,  the  extra  auricular  contraction  is  omitted, 
but  a  distinct  though  shortened  compensatory  pause  is  still  observed.  The 
phenomena  with  reversed  contraction  are  therefore  similar  to  those  seen  under 
the  usual  conditions.1 

Kaiser  finds  in  frogs  poisoned  with  muscarin  that  stimulation  of  the  ven- 
tricle during  the  refractory  period  causes  the  contraction  in  which  the  stimulus 
falls  to  be  more  complete,  as  shown  by  the  contraction  curve  rising  above  its 
former  level.  He  concludes  that  the  ventricle  is  not  wholly  inexcitable  even 
during  the  refractory  period. 

The  question  whether  the  refractory  state  and  compensatory  pause  are 
properties  of  the  muscle-substance  or  of  the  nervous  system  of  the  heart  has 
excited  considerable  attention.  If  the  ganglion-free  apex  of  the  frog's  ven- 
tricle is  stimulated  by  rapidly  repeated  induction  shocks  it  can  be  made  to  con- 
tract periodically  for  a  time.  By  momentarily  increasing  the  strength  of  any 
one  induction  shock  an  extra  stimulus  can  be  given  from  time  to  time.  When 
the  extra  stimulus  falls  after  the  contraction  maximum  or  during  diastole  an 
extra  contraction  results,  otherwise  not.  The  refractory  period  exists,  there- 
fore, independently  of  the  cardiac  ganglia. 

The  compensatory  pause  can  also,  though  not  always,  be  secured  with  the 
ganglion-free  apex.2 

The  refractory  period  has  been  used  to  show  how  a  continuous  stimulus 
might  produce  a  rhythmic  heart-beat.  The  continuous  stimulus  cannot  affect 
the  heart  during  tin;  refractory  period  from  the  beginning  to  near  the  maxi- 
mum of  systole.     At  the  close  of  the  refractory  period  the  constant  stimulus 

1  Kaiser  :  Zeitschrift  fur  Biologic,  L895,  xxxii.  p.  19. 

-Kaiser:  Ibid.,  p.  449;  for  experiments  on  the  embryo,  see  Pickering :  Journal  of  Physi- 
ology, 1896,  xx.  j>.  165. 


CIRCULATION.  159 

becomes  effective,  causing  an  extra  contraction  with  long  latent  period.  This 
latent  period  is,  according  to  this  theory,  the  interval  between  the  first  and  the 
second  contraction. 

A  tonic  contraction1  of  the  heart  muscle  is  sometimes  produced  by  strong, 
rapidly  repeated  induction  shocks  and  by  various  other  means,  such  as  filling 
the  ventricle  with  old  blood,  by  weak  sodium  hydrate  solution,  and  by  certain 
poisons,  such  as  digitalin  and  veratrin. 

A.  The   Cardiac  Nerves. 

The  cardiac  nerves  are  branches  of  the  vagus  and  the  sympathetic  nerves. 

In  the  dog  the  vagus  arises  by  about  a  dozen  fine  roots  from  the  ventro- 
lateral aspect  of  the  medulla  and  passes  outward  to  the  jugular  foramen  in 
company  with  the  spinal  accessory  nerve.  In  the  jugular  canal  the  vagus 
bears  a  ganglion  called  the  jugular  ganglion.  The  spinal  accessory  nerve 
joins  the  vagus  here,  the  spinal  portion  almost  immediately  leaving  the  vagus 
to  be  distributed  to  certain  muscles  in  the  neck,  while  the  medullary  portion 
passes  to  the  heart  through  the  trunk  ganglion  and  thereafter  in  the  substance 
of  the  vagus.  Directly  after  emerging  from  the  skull,  the  vagus  presents  a 
second  ganglion,  fusiform  in  shape  and  in  a  fairly  large  dog  about  one  centi- 
meter in  length.  From  the  caudal  end  or  middle  of  this  "  ganglion  of  the 
trunk "  is  given  off  the  superior  laryngeal  nerve,  slightly  behind  which  a 
large  nerve  is  seen  passing  from  the  sympathetic  chain  to  the  trunk  of  the 
vagus.  This  nerve  is  in  reality  the  main  cord  of  the  sympathetic  chain,  the 
sympathetic  nerve  being  bound  up  with  the  vagus  from  the  "  inferior"  cervical 
ganglion  to  the  point  just  mentioned.  Posterior  to  the  trunk  ganglion  of  the 
vagus,  the  vago-sympathetic  runs  caudalward  as  a  large  nerve  dorsal  to  the 
common  carotid  artery  as  far  as  the  first  rib  or  near  it,  where  it  enters  the 
so-called  inferior  cervical  ganglion.  This  ganglion  belongs  to  the  sympathetic 
system  and  not  to  the  vagus;  from  a  morphological  point  < if  view  it  is  the 
middle  cervical  sympathetic  ganglion.  The  true  inferior  cervical  sympathetic 
ganglion  is  fused  with  the  first  one  or  two  thoracic  ganglia  to  form  the  gan- 
glion stellatum,  situated  opposite  the  first  intercostal  space.  At  the  "  inferior 
cervical"  ganglion  the  vagus  and  the  sympathetic  part  company,  the  vagus 
passing  caudalward  behind  the  root  of  the  lung  and  the  sympathetic  passing 
to  the  stellate  ganglion,  dividing  on  its  way  into  two  portions  (the  annulus  of 
Yieussens),  which  embrace  the  subclavian  artery.  In  many  cases  the  lower 
loop  of  the  annulus  of  Vieussens  joins  the  trunk  of  the  vagus  caudal  to  the 
ganglion. 

The  cardiac  nerves  spring  from  the  vagus  and  the  sympathetic  nerve  in 
the  region  of  the  inferior  cervical  ganglion.  They  may  lie  divided  into  an 
inner  and  an  outer  group. 

The  inner  group  is  composed  of  one  medium,  one  thick,  and  two  or 
three  slender  nerves.     The  nerve  of  medium  thickness  springs  fr the  gan- 

1  Hunt,  Bookman,  and  Tierney:  CeniraJblait fur  Physiologic,  1897,  xi.  p.  274. 


100 


AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 


glion  itself.     The  thick  branch  rises  from  the  trunk  of  the  vagus  near  the 
origin  of*  the  inferior  laryngeal  nerve  about  1.25  centimeters  caudal  to  the 

inferior  cervical  ganglion.  It  can  be 
easily  followed  to  its  final  distribution. 
It  passes  behind  the  vena  cava  superior, 
perforates  the  pericardium,  and  runs 
parallel  with  the  ascending  aorta  across 
the  pulmonary  artery,  on  which  it  lies 
in  the  connective  tissue  already  divided 
into  two  or  three  tolerably  thick  twigs 
or  spread  in  a  fan  of  smaller  branches. 
These  now  bend  beneath  the  artery, 
pass  round  its  base  on  the  inner  side, 
and  reach  the  anterior  inter-ventricular 
groove.  Here  they  spread  over  the 
surface  of  the  ventricle.  The  slender 
branches  leave  the  vagus  trunk  caudal 
to  the  branch  just  described. 

The  outer  group  comprises  two  thick 
branches — namely,  an  upper  nerve, 
springing  from  the  ganglion  or  from 
the  trunk  of  the  vagus  near  it,  and  a 
lower  nerve,  from  the  lower  loop  of 
the  annulus,  or  from  the  vagus  1-1  £ 
centimeters  lower  down.  Each  of  these 
thick  branches  may  be  replaced  by  a 
bundle  of  finer  branches,  and  in  fact 
the  description  of  the  cardiac  nerves 
here  given  can  be  regarded  as  a  close  approximation  only,  so  frequent  are  the 
individual  variations.1 

In  the  rabbit  the  cervical  sympathetic  and  the  vagus  trunk  are  not  joined,  as 
in  the  dog,  but  run  a  separate  course.  Cardiac  fibres  from  the  spinal  cord  reach 
the  lower  cervical  and  first  thoracic  ganglion  (ganglion  stellatum)  along  their 
rami  eommunicantes  and  pass  to  the  heart  by  two  sympathetic  cardiac  nerves, 
one  from  the  interior  cervical  ganglion  and  one  from  the  ganglion  stellatum. 
The  arrangement  of  the  cardiac  nerves  in  the  cat  is  shown  in  Figure  29. 
In  the  frog  the  cardiac  nerves,  both  vagal  and  sympathetic,  reach  the  heart 
through  the  splanchnic  branch  of  the  vagus.  The  sympathetic  fibres  pass  out 
of  the  spinal  cord  with  the  third  spinal  nerve,  through  the  ramus  comniunicans 
of  this  nerve  into  the  third  sympathetic  ganglion,2  up  the  sympathetic  chain 
to  the  ganglion  of  the  vagus,  and  down  the  vagus  trunk  to  the  heart. 

1  Details  concerning  the  composition  of  the  cardiac  plexuses  in  the  dog  are  given  by  Lim 
Boon  Keng:  Journal  of  Physiology,  1893,  xiv.  p.  467. 

'  It  is  probable  that  the  fibres  of  spinal  origin  end  in  the  sympathetic  ganglia,  making  con- 
tacta  there  with  sympathetic  ganglion  cells,  the  axis-cylinder  processes  of  which  pass  up  the 
cervical  chain  and  descend  to  the  heart  in  company  with  the  vagus. 


-;-'  l 

Fig.  29.— Cardiac  plexus  and  stellate  ganglion 
of  the  cat,  drawn  from  nature  after  the  removal  of 
the  arteries  and  veins ;  about  one  and  one-half  times 
natural  size  (Boehm,  1875,  p.  258): 

R,  right;  /..left:  1,1,  vagus  nerve;  2,  cervical 
sympathetic  ;  2',  annulus  of  Vieussens  ;  2",  thoracic 
sympathetic;  3,  recurrent  laryngeal  nerve;  4,  de- 
pressor  nerve,  entering  the  vagus  on  the  right,  on 
the  left  running  a  separate  course  to  the  heart ; 
5,  middle  (often  called  "inferior")  cervical  gan- 
glion ;  5',  communicating  branch  between  middle 
cervical  ganglion  and  vagus  nerve;  6,  stellate  gan- 
glion; (I',  6"  6'",  spinal  roots  of  stellate  ganglion; 
7,  communication  between  stellate  ganglion  and 
vagus  ;  8',  8",  8'",  cardiac  nerves. 


CIRCULATION.  161 

The  connection  of  the  extrinsic  cardiac  nerves  with  the  intracardiac  mus- 
cle and  nerve-cells  is  not  yet  determined  satisfactorily.  ( lertain  fibres  in  the 
vagus,  said  to  be  derived  from  the  spinal  accessory  nerve,  terminate  in  "  end- 
baskets"  embracing  sympathetic  ganglion-cells,  the  axis-cylinder  processes 
of  which  end  on  the  cardiac  muscle-fibres.  Probably  the  inhibitory  action 
of  the  vagus  is  exercised  through  these  cells,  as  it  is  lost  in  animals  poisoned 
with  nicotine,  which  is  known  to  paralyze,  in  other  situations,  either  the  end- 
baskets  about  sympathetic  cells  or  the  body  of  the  cell  itself.  Other  vagus 
fibres  apparently  terminate  (or  arise)  in  an  end-brush  in  the  pericardium  and 
endocardium. 

The  augmentor  apparatus  consists  of  two,  possibly  three,  neurons.  The 
cell-body  of  one  lies  in  the  spinal  cord ;  its  axis-cylinder  process  leaves  the 
cord  in  the  white  ramus  and  terminates  in  a  ganglion  of  the  sympathetic  chain 
(inferior  cervical,  stellate  ganglion).  The  axis-cylinder  process  of  the  sympa- 
thetic ganglion-cell  passes  directly  to  the  cardiac  muscle-fibre  on  which  it 
ends,  or,  possibly,  terminates  in  physiological  contact  with  the  dendrites  of  a 
third  neuron  lying  in  the  heart,  the  neuraxon  of  which  carries  the  augment- 
ing impulse  to  the  muscle-cell.  Stimulation  of  the  white  ramus  causes  aug- 
mentor effects.  In  nicotine-poisoning,  these  effects  cannot  be  obtained  ;  but 
stimulation  on  the  distal  side — the  cardiac  side — of  the  cell-body  about  which 
the  neuraxon  ends,  still  causes  augmentation.  If  nicotine  paralyzes  the 
sympathetic  cell-body,  this  experiment  proves  that  there  is  no  cell  in  this 
neuron  chain  between  the  point  stimulated  and  the  muscle-fibre  ;  if  it  par- 
alyzes the  end-basket  and  not  the  cell-body,  the  existence  of  the  third  (intra- 
cardiac) neuron  in  the  chain  is  possible,  provided  the  communication  between 
the  second  and  the  third  neuron  is  not  by  means  of  an  end-basket  ;  but,  as 
Dogiel  and  Huber  assume,  by  a  contact  with  the  dendrites,  similar  to  that 
observed  by  them  in  other  sympathetic  cells,  and  not  sensitive  to  nicotine. 

The  Inhibitory  Nerves. 

In  1845,  Ernst  Heinrich  and  Eduard  Weber  announced  that  stimulation 
of  the  vagus  nerves  or  the  parts  of  the  brain  where  they  arise  slows  the  heart 
even  to  arrest.  When  one  pole  of  an  induction  apparatus  was  placed  in  the 
nasal  cavity  of  a  frog  and  the  other  on  the  spinal  cord  at  the  fourth  or  fifth 
vertebra,  the  heart  was  completely  arrested  after  one  or  two  pulsations  and 
remained  motionless  several  seconds  after  the  interruption  of  the  current. 
During  the  arrest,  the  heart  was  relaxed  and  filled  gradually  with  blood. 
When  the  stimulus  was  continued  many  seconds,  the  heart  began  to  beat  again, 
at  first  weakly  and  with  long  intervals,  then  more  strongly  and  frequently, 
until  at  length  the  beats  were  as  vigorous  and  as  frequent  as  before,  though  all 
this  time  the  stimulation  was  uninterrupted. 

In  order  to  determine  from  what  part  of  the  brain  this  influence  proceed-, 
the  electrodes  were  brought  very  near  together  and  placed  upon  the  cerebral 
hemispheres.  The  movements  of  the  hear!  were  not  affected.  Negative  results 
followed  also  the  stimulation  of  the  spinal  cord.    Not  until  the  medulla  oblon- 

VOL.    I.— 11 


162 


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gata  between  the  corpora  quadrigernina  and  the  lower  end  of  the  calamus  scrip- 
torius  was  stimulated  did  the  arrest  take  place.  Cutting  away  the  spinal  cord 
and  the  remainder  of  the  brain  did  not  alter  the  result. 

Having  determined  that  the  inhibitory  power  had  its  seat  in  the  medulla 
oblongata,  the  question  arose  through  what  nerve  the  inhibitory  influence  is 
transmitted  to  the  heart.  In  a  frog  in  which  the  stimulation  of  the  medulla 
had  stopped  the  heart,  the  vagus  nerves  were  cut  and  the  ends  in  connection 
with  the  heart  stimulated.     The  heart  was  arrested  as  before. 

Thus  the  fundamental  fact  of  the  inhibition  of  a  peripheral  motor  mechan- 
ism by  the  central  nervous  system  through  the  agency  of  special  inhibitory 


Fig.  30.— Pulsations  of  frog's  heart,  inhibited  by  the  excitation  of  the  left  vagus  nerve  (Tarchanoff, 
1876,  p.  296):  C,  pulsations  of  heart ;  6,  electric  signal  which  vibrated  during  the  passage  of  the  stimu- 
lating current,  one  vibration  for  each  induction  shock. 

nerves  was  firmly  established.  A  great  number  of  investigations  have  demon- 
strated that  this  inhibitory  power  is  found  in  many  if  not  all  vertebrates  and 
not  a  few  invertebrates. 

The  effect  of  vagus  stimulation  on  the  heart  is  not  immediate ;  a  latent 
period  is  seen  extending  over  one  beat  and  sometimes  two,  according  to  the 
moment  of  stimulation  (see  Fig.  30). 


Fig.  31.—  Showing  the  lengthened  diastole  and  diminished  force  of  ventricular  contraction  during 
weak  stimulation  of  the  peripheral  end  of  the  cut  vagus  nerve.  The  heart  (cat)  was  isolated  from  both 
Bystemic  and  pulmonary  vessels,  and  was  kept  beating  by  circulating  defibrinated  blood  through  the 
coronary  arteries :  A,  Pressure  in  lefl  ventricle,  which  was  filled  with  normal  saline  solution,  and  com- 
municated  with  a  Bilrthle  membrane  manometer  by  means  of  a  cannula  which  was  passed  through  the 
auricular  appendix  and  the  mitral  orifice;  B,  line  drawn  by  the  armature  of  an  electro-magnet  in  the 
primary  circuit ;  the  heavy  line  indicates  the  duration  <>f  stimulation  ;  C,  time  in  seconds. 

Changes  in  the  Ventricle. — The  periodicity  of  the  ventricular  contraction 
is  altered  by  vagus  excitation,  a  weak  excitation  lengthening  the  duration  of  dias- 
tole, while  leaving  the  duration  of  systole  unchanged  (see  Fig.  31).  A 
stronger  excitation,  capably  of  modifying  largely  the  force  of  the  contraction, 
Lengthens  both  Bystole  and  diastole.1     The  difficulty  of  producing  a  continued 

'Meyer:   Archives  de  Phy$iologie,  1894,  p.  698;  Arloinij:  Ibid.,  p.  88. 


CIR  C  ULA  TIOX.  1 63 

arrest  in  diastole  is  much  greater  in  some  animals  than  in  others.  Even  when 
easily  produced,  the  arrest  soon  gives  away  in  the  manner  described  by  E.  H. 
and  E.  Weber,  the  heart  beginning  to  beat  in  spite  of  the  vagus  excitation.1 

The  force  of  the  contraction,  measured  by  the  height  of  the  up-stroke  of  the 
intra-ventricular  pressure  curve,  or  by  placing  a  recording  lever  on  the  heart, 
is  lessened,  this  diminution  in  force  appearing  often  before  any  noticeable 
change  in  periodicity. 

The  diastolic  pressure  increases,  as  is  shown  by  the  lower  level  of  the  curve 
gradually  rising  farther  and  farther  above  the  atmospheric  pressure  line. 

The  volume  of  blood  in  the  ventricle  at  the  close  of  diastole  is  increased.  So 
also  is  the  volume  at  the  close  of  systole  (residual  blood) — sometimes  to  such 
a  degree  that  the  volume  of  the  heart  at  the  end  of  systole  may  be  greater  than 
the  volume  of  the  organ  at  the  end  of  diastole  before  the  vagus  was  excited. 

The  output  and  the  input  of  the  ventricle,  that  is,  the  quantity  of  blood  dis- 
charged and  received,  are  both  diminished  by  vagus  excitation. 

The  ventricular  tonus,  or  state  of  constant  slight  contraction  on  which  the 
systolic  contractions  are  superimposed,  is  also  diminished,  as  is  well  shown  by 
an  experiment  of  Stefani.2  In  this  experiment  the  pericardial  sac  is  filled  with 
normal  saline  solution  under  a  pressure  just  sufficient  to  prevent  the  expansion 
of  the  heart  in  diastole.  On  stimulation  of  the  vagus,  the  heart  dilates  fur- 
ther. A  considerably  higher  pressure  is  necessary  to  overcome  this  dilatation. 
Stefani  finds  also  that  the  pressure  necessary  to  prevent  diastolic  expansion  is 
much  greater  with  intact  than  with  cut  vagi.  Furthermore,  the  heart  is  much 
more  easily  distended  by  the  rise  of  arterial  pressure  through  compression  of 
the  aorta  when  the  vagi  are  severed  than  when  they  are  intact.  Franck  has 
noticed  that  the  walls  of  the  empty  ventricle  become  softer  when  the  vagus  is 
stimulated.3 

The  propagation  of  the  cardiac  excitation  is  more  difficult  during  vagus 
excitation.  JBayliss  and  Starling  demonstrate  this  on  mammalian  hearts 
made  to  contract  by  exciting  the  auricle  three  or  four  times  per  second  ;  the  ven- 
tricle as  a  rule  responds  regularly  to  every  auricular  beat.  If,  then,  the  vagus 
is  stimulated  with  a  weak  induced  current,  the  ventricle  may  drop  every  other 
beat,  or  may  for  a  short  time  cease  to  respond  at  all  to  the  auricular  contrac- 
tions. The  defective  propagation  is  not  due  to  changes  in  the  auricular  con- 
traction, for  even  an  almost  inappreciable  beat  of  the  auricle  can  cause  the 
ventricle  to  contract.  Nor  is  it  due  to  lowered  excitability  of  the  ventricle, 
for  the  effect  described  is  seen  with  currents  too  weak  to  depress  the  irrita- 
bility of  the  ventricle  to  an  appreciable  extent. 

The  sino-auricular  and  auriculo-ventricular  contraction  intervals  arc  usu- 
ally lengthened   by  vagus  excitation  ;   sometimes,  however,   they  are  dimin- 

1  Hough:  Journal  of  Physiology,  1895,  xviii.  p.  Kit.  The  terrapin  heart  is  said  not  t<>  es- 
cape, as  a  rule,  from  vagus  inhibition. 

2  Compare  Stefani :   Archives  italiennes  de  Biologie,  1895,  sxiii.  p.  175. 

3  .See  also  Fischel :  Archiv  fur  experimentelk  Palhologie  und  Pharmakologie,  L897,  \\\\iii. 
p.  228. 


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AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 


ished  ;  the  one  may  be  increased,  while  the  other  is  diminished.  The  vagus 
effect  quickly  reaches  a  maximum  and  then  slowly  decreases.  The  interval 
between  the  contractions  of  different  parts  of  the  sinus  is  sometimes  increased 
by  vagus  excitation,  so  that  the  different  parts  are  dissociated  and  heat  at 
measurably  different  times.  Attempts  have  been  made  to  explain  the  sev- 
eral actions  of  the  vagus  nerve,  together  with  the  various  forms  of  intermit- 
tent ami  irregular  pulse,  by  variations  in  the  transmission  of  the  cardiac  ex- 
citation ; '  hut  it  is  probable  that  alterations  in  the  condition  of  the  muscle-cells 
in  the  sinus,  auricle,  and  ventricle  are  of  equal  or  greater  importance.2 

The  action  of  the  vagus  is  accompanied  by  an  electrical  variation.  This 
has  been  shown  in  the  muscular  tissue  of  the  resting  auricle  of  the  tortoise 
(see  Fig.  32).  The  auricle  is  cut  away  from  the  sinus  without  injuring  the 
coronary  nerve,  which  in  the  tortoise  passes  from  the  sinus  to  the  auricle  and 
contains  the  cardiac  fibres  of  the  vagus.  After  this  operation  the  auricle  and 
ventricle  remain  motionless  for  a  time,  and  this  quiescent  period  is  utilized  for 
the  experiment.  The  tip  of  the  auricle  is  injured  by  immersion  in  hot  water, 
and  the  demarcation  current  (the  injured  tissue  being  negative  toward  the  unin- 
jured) is  led  off  to  a  galvanometer.  On  exciting  the  vagus  in  the  neck,  the 
demarcation  current  is  markedly  increased.  No  visible  change  of  form  is  seen 
in  the  auricular  strip. 


Fig.  32.— The  tortoise  heart  prepared  for  the  demonstration  of  the  electrical  change  in  the  cardiac 
muscle  accompanying  the  excitation  of  the  vagus  nerve:  t',  vagus  nerve;  C,  coronary  nerve;  S,  sinus 
and  part  of  auricle  in  connection  with  it ;  (7,  galvanometer,  in  the  circuit  formed  by  two  uon-polarizable 
electrodes  and  the  part  of  the  auricle  between  them  ;  /■-',  induction  coil  (Gaskell,  1887). 

Changes  in  the  Sinus  and  Auricle. — There  is  little  probability  that  the 
action  of  the  vagus  on  the  sinus  and  auricle,  or  greal  veins,3  differs  essentially 

from  the  action  on  the  ventricle.      The  force  of  the  contraction  is  diminished. 


1  Muskens:   American  Journal  of  Phygiolor/t/,  1 898,  i.  p.  486. 
-  Bofmann  :   Archivfur  'lit  <\,~<nini,i,   Vhy/iuhiijie,  1898,  lxxii.  p.  409. 

3  Knoll  :  Archiv  fur  die  gesammL  Physiologie,  1897,  lxviii.  p.  839;  Engelmann:  Ibid.,  1896, 
lxv.  p.  109. 


CIR  CULA  TION.  165 

The  diastole  is  lengthened.  The  change  in  force  appears  earlier  than  the 
change  in  periodicity,  and  sometimes  without  it.  On  the  whole,  the  sinus  and 
auricle  are  more  easily  affected  bv  vastus  excitation  than  the  ventricle. 

Action  on  Bulbus  Arteriosus. — If  the  bulbus  arteriosus  of  the  frog's 
heart  is  extirpated  in  such  a  way  as  to  leave  untouched  the  nerve-fibres  that 
connect  it  with  the  auricular  septum,  the  contractions  of  the  isolated  bulbus 
will  be  arrested  when  the  peripheral  end  of  the  vagus  is  excited.1 

Diminished  Irritability  of  Heart. — During  vagus  excitation  with  cur- 
rents of  moderate  strength,  the  arrested  heart  will  respond  to  direct  stimula- 
tion by  a  single  contraction.  With  strong  vagus  excitation,  however,  the 
directly  stimulated  heart  contracts  not  at  all  or  less  readily  than  before. 

Effects  of  Varying  the  Stimulus. — A  single  excitation  of  the  vagus  does 
not  stop  the  heart.  Morat  has  investigated  the  effect  of  excitations  of  varied 
duration,  number,  and  frequency  on  the  tortoise  heart.2  With  excitations  of 
the  same  duration,  the  effect  was  minimal  at  2  per  second,  maximal  at  7 
per  second,  diminishing  thereafter  as  the  frequency  increased.  The  longer  the 
stimulation,  the  longer  (within  limits)  was  the  inhibition.  An  excitation  that 
is  too  feeble  or  too  slow,  or,  on  the  contrary,  is  over-strong  or  over-frequent, 
has  no  effect.  Within  limits,  however,  the  degree  of  inhibition  increases  witli 
the  strength  of  the  stimulus. 

Weak  stimuli  affect  primarily  the  auricles,  diminishing  frequency  and  force 
of  contraction,  and  secondarily  lower  the  frequency  of  the  ventricle.  Stronger 
stimuli  arrest  the  auricle,  the  ventricles  continuing  to  beat  with  almost  undi- 
minished force  but  with  altered  rhythm.  Still  stronger  stimuli  inhibit  the 
ventricles  also. 

The  frequency  can  be  kept  comparatively  small  by  continued  moderate 
stimulation. 

Arrest  in  Systole. — The  excitation  of  the  tortoise  vagus  in  the  upper  or 
middle  cervical  region  is  sometimes  followed,  according  to  Rouget,3  by  a  state 
of  continued,  prolonged  contraction — in  short,  an  arrest  in  systole.  The  same 
effect  is  observed  in  rabbits  strongly  curarized  and  in  curarized  frogs.  Arloing  ' 
noticed  that  the  mechanical  irritation  produced  by  raising  on  a  thread  the  left 
vagus  nerve  of  a  horse  caused  the  right  ventricle  to  remain  contracted  during 
seven  seconds.  The  ventricular  curve  during  this  time  presented  the  characters 
of  the  tetanus  curve  of  a  skeletal  muscle.  Recent  observations  by  Frank,8 
Hunt,6  Walther,7  and  others  make  it  probable  that  a  kind  of  summation  and 
superposition  of  contractions  may  at  times  take  place  in  the  heart  as  in 
ordinary  striated   muscular  tissue. 

1  Dogiel:  Centralblatt  fur  die  medieinischen  Wissenschaften,  L894,  p.  227. 

2  Morat:  Archives  </>•  Physiologie,  L894,  p.  10. 
3Kouget:   I  hid.,  p.  398. 

*  Arloing:   Ibid.,  L893,  y.  112. 

5  Frank  :  Zeitschrift  fur  Biologie,  1899,  xxxviii. 

6  Hunt,  Bookman,  ami  Tierney:   Centralblatt  fur  Physiologie,  1897,  xi.  p.  274. 

7  Walther  :  Archivfur  die  gesammte  Physiologie,  1900,  lxxviii.  p.  597. 


L66  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

Comparative  Inhibitory  Power. — One  vagus  often  possesses  more  inhibi- 
tory power  than  the  other.1 

Septal  Nerves  in  Frog. — The  electrical  stimulation  of  the  peripheral 
stump  of  either  of  two  large  nerves  of  the  inter-auricular  septum  in  the  frog 
alters  the  tonus  and  the  force  of  contraction  of  the  ventricle,  but  not  the  fre- 
quency. After  section  of  these  nerves,  the  excitation  of  the  vagus  has  very 
little  effect  on  the  tonus,  and  almost  none  on  the  force  of  the  ventricular  beat, 
while  the  frequency  is  diminished  in  the  characteristic  manner.  Evidently, 
therefore,  the  two  large  septal  nerves  take  no  part  in  the  regulation  of  fre- 
quency, but  leave  this  to  the  nerves  diffusely  distributed  through  the  auricles. 
There  i<  then  an  anatomical  division  of  the  septal  branches  of  the  frog's  vagus, 
the  fibres  affecting  periodicity  running  outside  the  septal  nerves,  while  those 
uaodifying  the  force  of  contraction  and  thetonusof  the  ventricle  run  within  them.2 

Nature  of  Vagns  Influence  on  Heart. — The  nature  of  the  terminal 
apparatus  by  which  the  vagus  inhibits  the  heart  is  unknown.  It  is  probable 
that  the  same  intracardiac  apparatus  serves  for  both  nerves,  for  Hurler  finds 
that  when  the  heart  escapes  from  the  inhibition  caused  by  continued  stimula- 
tion of  one  vagus,  the  prolonged  diastole  growing  shorter  again,  the  immediate 
stimulation  of  the  second  vagus  has  no  effect  upon  the  heart.3  Dogiel  and 
Grahe  have  recently  observed  that  the  lengthening  of  diastole  which  follows 
stimulation  of  the  peripheral  stump  of  the  vagus,  the  other  vagus  being  intact, 
is  less  marked  than  when  both  vagi  are  cut.4 

The  earlier  attempts  to  form  a  satisfactory  theory  for  the  inhibitory  power 
of  the  vagus  met  with  little  success.  The  statement  of  the  Webers'  that  the  vagus 
inhibits  the  movements  of  the  heart  gave  to  nerves  a  new  attribute,  but  is 
hardly  an  explanation.  The  view  of  Budge  and  Schiff,  that  the  vagus  is  the 
motor  nerve  of  the  heart  and  that  inhibition  is  the  expression  of  its  exhaustion, 
is  now  of  only  historical  iutere.-t.  Nor  has  a  better  fate  overtaken  the  theory 
of  Brown-Sequard,  who  saw  in  the  vagus  the  vaso-motor  nerve  of  the  heart, 
the  stimulation  of  which,  by  narrowing  the  coronary  arteries,  deprived  the 
heart  of  the  blood  that,  according  to  Brown-Sequard,  is  the  exciting  cause  of  the 
contraction. 

Of  recent  years,  the  explanation  that  has  commanded  most  attention  is  the 
one  advanced  by  Stefan  i ''  andGaskell,  namely,  that  the  vagus  is  the  trophic  nerve 
of  the  heart,  producing  a  dis-assimilation  or  katabolism  in  systole  and  an 
as-imilation  or  anabolism  in  diastole.  Gaskell  supports  this  theory  by  the 
observation  that  the  after-effect  of  vagus  excitation  is  to  strengthen  the  force 
of  the  cardiac  contraction  and  to  increase  the  speed  with  which  the  excitation 

1  Ilofinann:  Archie  fiir  die  gegammte  Physiologic,   1895,  lx.  p.  169. 

3  For  other  unusual  alterations  in  the  heart-beat  in  consequence  of  vagus  excitation  see 
Arloing:  Archives  <{■•  I'fui.tioloijie,  18U4,  p.  lti:;;  and  Knoll:  Archil)  fiir  die  gesammte  Physiologic, 
1897,  Ixvii.  p.  587. 

3  Hough     Journal  of  Physiology,  1895,  xviii.  p.  198. 

*  Dogiel  and  Grahe:  Archiv  fur  Physiologie,  1895,  p.  393.  Changes  in  the  peripheral  effi- 
ciency of  the  vagi  are  discussed  by  McWilliams  :    Proceedings  Royal  Society,  1893,  liii.  p.  475. 

5  Stefani :  Archives  italiennesde Biologie,  1895,  xxiii.  p.  17G. 


CIR  CULA  TION.  167 

wave  passes  over  the  heart,  while  the  contrary  effects  are  witnessed  after  the 
excitation  of  the  augmentor  nerves. 

Various  attempts  have  been  made  to  prove  a  trophic  action  of  the  vagus  on 
the  heart  by  cutting  the  nerve  in  animals  kept  alive  until  degenerative  changes 
in  the  heart-muscle  should  have  had  time  to  appear.  The  important  distribu- 
tion of  the  vagus  nerve  to  many  organs,  and  the  consequently  wide  extent  of 
the  loss  of  function  following  its  section,  makes  it  difficult  to  decide  whether  the 
changes  produced  in  the  heart  are  not  secondary  to  the  alterations  in  other  tis- 
sues. The  work  of  Fantino  will  serve  for  an  example  of  these  investigations. 
Fantino  cut  a  single  vagus  to  avoid  the  paralysis  of  deglutition  and  the  inani- 
tion and  occasional  broncho-pneumonia  that  follow  section  of  both  nerves. 
Young  and  perfectly  healthy  rabbits  and  guinea-pigs  were  selected.  The  opera- 
tion was  strictly  aseptic,  and  all  cases  in  which  the  wound  suppurated  were 
excluded.  A  piece  of  the  nerve  about  one  centimeter  long  was  cut  out,  so  that 
no  reunion  could  be  possible.  After  the  operation  the  animals  were  as  a  rule 
lively,  ate  well,  and  gained  weight.  Post-mortem  examination  of  animals 
killed  two  days  or  more  after  section  of  the  vagus  nerve  disclosed  no  patho- 
logical changes  in  the  lungs,  spleen,  liver,  and  stomach.  In  the  heart,  areas 
were  found  in  which  the  nuclei  and  the  striation  of  the  muscle-cells  had  disap- 
peared. Eighteen  days  after  section  the  atrophy  of  the  cardiac  muscle  in  these 
areas  was  observed  to  be  extreme.  The  degenerations  following  section  of  the 
right  vagus  were  situated  in  a  different  part  of  the  ventricular  wall  from  those 
following;  section  of  the  left  nerve. 

The  effects  of  stimulation  of  the  vagus  nerve  in  the  new-born  do  not  differ 
essentially  from  those  seen  in  the  adult.1 

The  relation  between  the  action  of  the  vagus  and  (lie  intracardiac  pressure 
has  been  recently  studied  by  Stewart.  He  finds  that  an  increase  in  the  pressure 
in  the  sinus  or  auricle  makes  it  difficult  to  inhibit  the  heart  through  the  vagus. 

The  inhibitory  action  of  the  vagus  diminishes  as  the  temperature  of  the 
heart  falls.  At  a  low  limit  the  inhibitory  power  is  lost,  but  may  return  when 
the  heart  is  warmed  again.  Even  when  the  stimulation  of  the  trunk  of  the 
nerve  has  failed  to  affect  the  cooled  heart,  the  direct  stimulation  of  the  sinus 
can  still  cause  distinct  inhibition.  The  power  of  inhibiting  the  ventricle  is 
first  lost.  Loss  of  inhibitory  power  does  not  follow  the  raising  of  the  heart 
to  high  temperatures.  The  vagus  remains  active  to  the  verge  of  heat  arrest, 
mid  resumes  it.^  power  as  soon  ;is  the  temperature  is  lowered. 

The  Augmentor  Nerves. 
v.  Bezold  observed  in  1862  that  stimulation  of  the  cervical  spinal  cord 
caused  an  increased  frequency  of  heart-beat.  This  seemed  to  him  to  prove 
the  existence  of  special  accelerating  nerves.  Ludwig  and  Thiry,  however, 
soon  pointed  out  that  stimulation  of  the  spinal  cord  in  the  cervical  region 
excited  many  vaso-constrictor  fibres,  leading  to  the  narrowing  of  many  vessels 
and  a  corresponding  rise  of  blood-pressure.  The  acceleration  of  the  heart-beal 
'Meyer:  A  rehire*  tie  Phyaiolngie,  1893,  p.  477. 


168 


AN   AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 


accompanying  this  rise  in  blood-pressure  would  alone  explain  the  observation 
of  von  Bezold.  Three  years  later  Bever  and  von  Bezold  were  more  suc- 
cessful. The  influence  of  the  vaso-motor  nerves  was  excluded  by  section  of 
the  spinal  cord  between  the  first  and  second  thoracic  vertebrae.  Stimulation 
of  the  cervical  cord  now  caused  an  increase  in  the  frequency  of  the  heart-beat 
without  a  simultaneous  increase  of  blood-pressure.  The  fibres  carrying  the 
accelerating  impulse  were  traced  from  the  spinal  cord  to  the  last  cervical  gan- 
glioD  and  from  there  toward  the  heart. 

In  the  dog  the  "  augmenting "  or  "  accelerating "  nerves  thus  discovered 
leave  the  spinal  cord  mainly  by  the  roots  of  the  second  dorsal  nerves,  and  enter 
the  ganglion  stellatum,  whence  they  pass  through  the  anterior  and  posterior 
loops  of  the  annulus  of  Vieussens  into  the  inferior  cervical  ganglion,  from 
which  they  go,  in  the  cardiac  branches  of  the  latter,  to  the  heart.  Some  of 
the  cardiac  fibres  in  the  annulus  pass  directly  thence  to  the  cardiac  plexus  and 
do  not  enter  the  inferior  cervical  ganglion. 

In  the  rabbit,  the  course  of  the  augmentor  fibres  is  probably  closely  similar 
to  that  in  the  dog. 

In  the  cat,  the  augmentor  nerves  spring  from  the  ganglion  stellatum,  and 
very  rarely  from  the  inferior  cervical  ganglion  as  well.  The  right  cardiac 
sympathetic  nerve  communicates  with  the  vagus. 

The  stimulation  of  the  sympathetic  chain  in  the  frog,  "  between  ganglion  1 
and  the  vagus  ganglion,  and  also  stimulation  of  the  chain  between  ganglia  2 

and  3,  causes  marked  acceleration  and 
augmentation  of  the  auricular  and  ven- 
tricular contractions.  Stimulation  be- 
tween ganglia  3  and  4  produces  no  effect 
whatever  upon  the  heart."  This  ex- 
periment of  Gaskell  and  Gadow's  shows 
that  augmentor  fibres  enter  the  sympa- 
thetic from  the  spinal  cord  along  the 
ramus  communicans  of  the  third  spinal 
nerve  and  pass  upward  in  the  sympa- 
thetic chain.  In  this  animal  the  sym- 
pathetic chain,  after  dividing  between 
the  first  and  second  ganglia  to  form  the 
annulus  of  Vieussens,  joins  the  trunk 
of  the  vagus  between  the  united  vagus 
and  glosso-pharyngeal  ganglia  and  the 
vertebral  column  (see  Fig.  33).  Here  the  sympathetic  again  divides,  some  of 
the  fibre-  passing  alongside  the  vagus  into  the  cranial  cavity,  the  rest  accompany- 
in-  the  vagus  nerve  peripherally.  The  augmentor  nerve-  for  the  heart  are 
amonar  the  latter,  for  the  stimulation  of  the  intracranial  vagus  results  in  pure 
inhibition,  while  the  stimulation  of  the  vagus  trunk  after  it  is  joined  by  the 
sympathetic  may  give  either  inhibition  or  augmentation.  We  may  say.  there- 
fore, that  the  augmentor  nerves  of  the  frog  pass  out  of  the  spinal   cord   by  the 


V-Sy 


Fig.  33.— The  cardiac  sympathetic  nervt-  in 

Rana    temporalis    (twice    natural   size):    V-Sy, 

mpathetic;  A.v,  arteria  vertebralis;  II, 

TV,  second  and   fourth  spinal  nerves   (.Gaskell 

ami  Oa.low,  lsMj. 


CIRCULATION. 


169 


third  spinal  nerve,  through  the  ramus  communicans  of  this  nerve,  into  the 
third  sympathetic  ganglion,  up  the  sympathetic  chain  to  the  ganglion  of  the 
vagus,  and  down  the  vagus  trunk  to  the  heart. 

Stimulation  of  Augrnentor  Nerves. — The  most  obvious  effect  of  the  stim- 
ulation of  the  augrnentor  nerves  is  an  increase  of  from  7  to  70  per  cent,  in  the 
frequency  of  the  heart-beat  (see  Fig.  34).  The  quicker  the  heart  is  beating 
before  the  stimulation,  the  less  marked  is  the  acceleration.     The  absolute  maxi- 


Fig.  34.— Curve  of  blood-pressure  in  the  cat,  recorded  by  a  mercury  manometer,  showing  the 
increase  in  frequency  of  heart-beat  from  excitation  of  the  augrnentor  nerves.  The  curve  reads  from 
right  to  left.  The  augrnentor  nerves  were  excited  during  thirty  seconds,  between  the  two  stars.  The 
number  of  beats  per  ten  seconds  rose  from  24  to  33  (Boehm,  1875,  p.  258). 

mum  of  frequency  is,  however,  independent  of  the  frequency  before  stimulation. 
The  maximum  of  acceleration  is  largely  independent  of  the  duration  of  stimula- 
tion.    The  duration  of  stimulation  and  the  duration  of  acceleration  are  not 
related,  a  long  stimulation  causing  no  greater  acceleration  than  a  short  one. 

The  force  of  the  ventricular  beat  is  increased.  The  ventricle  is  filled  more 
completely  by  the  auricles,  the  volume  of  the  ventricle  being  increased.     The 


JSrcJfJV.yice.y 


Fig.  35.— Increase  in  the  force  of  the  ventricular  contraction  (curve  of  pressure  in  right  ventricle)  from 
stimulation  of  augrnentor  fibres.    There  is  little  or  no  change  in  frequency  (Franck,  1890,  p.  819). 

output  of  the  heart  is  raised.  There  is  no  definite  relation  between  the  in- 
crease of  contraction  volume  or  force  of  contraction  and  the  increase  in  fre- 
quency (see  Fig.  35).  Either  may  appear  without  the  other,  though  this  is 
rare.  The  simultaneous  stimulation  of  the  nerves  of  both  sides  does  not 
give  a  greater  maximum  frequency  than  the  stimulation  of  one  nerve 
alone. 

The  strength  and  the  volume  of  the  auricular  contractions  are  also  in- 
creased. The  increase  in  volume  is  not  due  to  a  rise  of  pressure  in  the  veins 
— in  fact,  the  pressure  falls  in  the  veins — but  to  a  change  in  the  elasticity  of 
the  relaxed  auricle,  a  lowering  of  its  tonus.  This  change  is  not  related  to  the 
increase  in  the  force  of  the  auricular  contractions  that  stimulation  of  the  aug- 
rnentor nerves  also  causes.  It  varies  much  in  amount  and  i-  less  constantly 
met  with  than  the  change  in  force.      The  changes  in  the  ventricle  and  auricle 


170  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

probably  account  for  the  rise  of  blood-pressure  in  the  systemic  arteries  and  the 
fall  in  both  systemic  and  pulmonary  veins  observed  by  Roy  and  Adami. 

The  speed  of  the  cardiac  excitation  waive  is  increased.  Its  passage  across 
the  auriculo-ventricular  groove  is  also  quickened,  as  is  shown  in  the  following 
experiment  of  Bayliss  and  Starling.  In  the  dog,  the  artificial  excitation  of 
the  ventricle  may  cause  the  excitation  wave;  to  travel  in  a  reverse  direction, 
namely,  from  ventricle  to  auricle.  If  the  ventricles  are  excited  rhythmically 
and  the  rate  of  excitation  is  gradually  increased,  a  limit  will  be  reached  beyond 
which  the  auricle  no  longer  beats  in  response  to  every  ventricular  contraction. 
With  intact  vagi,  a  rate  of  3  per  second  is  generally  the  limit.  If  now  the 
augmentor  nerve  is  stimulated,  the  "block"  is  partially  removed,  and  the 
auricle  beats  during  and  for  a  short  time  after  the  stimulation  at  the  same 
rapid  rate  as  the  ventricle. 

The  Intent  period  of  the  excitation  is  long.  In  the  dog,  about  two  seconds 
pass  between  the  beginning  of  stimulation  and  the*  beginning  of  acceleration, 
and  ten  seconds  may  pass  before  the  maximum  acceleration  is  reached.  The 
after-effect  may  continue  two  minutes  or  more.  It  consists  of  a  weakening  of 
the  contractions  and  an  increase  in  the  difficulty  with  which  the  excitation 
wave  passes  from  the  auricle  to  the  ventricle.  The  return  to  the  former  fre- 
quency is  more  rapid  after  short  than  after  long  stimulations. 

The  effect  upon  the  heart-rate  of  simultaneous  stimulation  of  the  vagi  and 
accelerator  nerves,  according  to  Hunt,  is  determined  by  the  relative  strength 
of  the  two  stimulating  currents.  For  sub-maximal  stimuli  the  result  for 
both  systole  and  diastole  is  approximately  the  arithmetical  mean  of  the  re- 
sults of  stimulating  the  two  nerves  .separately.'  The  acceleration  that  is  seen 
after  the  stimulation  of  the  vagus  is  due  to  the  after-effect  of  the  stimulation 
of  accelerating  fibres  in  the  vagus. 

The  simultaneous  stimulation  of  the  augmentors  and  the  vagi,  the  strength 
of  the  current  being  sufficient  to  stop  the  auricular  contractions,  causes  accel- 
eration of  the  ventricular  contractions. 

The  acceleration  of  the  heart  may  be  more  or  less  intermittent,  although 
the  excitation  of  the  augmentor  nerves  continues.  It  is  probable  that  this  is 
due  to  irradiation  from  the  bulbar  respiratory  centre.2 

Other  Centrifugal  Heart-nerves. 

In  the  vago-sym pathetic  trunk  and  the  annulus  of  Vieussens  fibres  pass  to 
the  heart  that  cannot  he  classed  either  with  the  vagus  or  the  augmentor  nerves. 
The  evidence  for  their  existence  is  furnished  by  Hoy  and  Adami's  observation 
that  when  the  intracardiac  vagus  mechanism  is  acting  strongly,  so  that  the 
auricles  are  more  or  less  completely  arrested,  the  stimulation  of  the  vago- 
sympathetic trunk  sometimes  causes  a  decided  increase  in  the  force  both  of 
the  ventricles  and  the  auricles,  usually  accompanied  by  an  acceleration  of  the 
rhythm  of  the  heart.  These  changes  are  too  rapidly  produced  to  be  aug- 
mentor effects. 

1  I  I  nut  :    Aini'rinni  Journal  of  l'lii/xio!o</it,  1899,  ii.  p.  422. 

2  Werthemier  and  Lepage  :  Journal  de  phygiologie  et  cle  pathologic  generate,  1899,  p.  236. 


CIRCULATION. 


171 


Centrifugal  inhibitory  nerves  have  been  found  as  an  anomaly  in  the  right 
depressor  nerve  of  a  rabbit.1 

Pawlow  divides  the  inhibitory  and  augmentor  nerves  into  four  classes — 
(1)  nerves  inhibiting  the  frequency  of  the  beat,  (2)  nerves  inhibiting  the  force  of 
the  contraction,  (3)  nerves  augmenting 
frequency,  and  (4)  nerves  augmenting 
force.  The  origin  of  this  subdivision 
of  the  two  groups  generally  recog- 
nized was  the  observation  that,  in  cer- 
tain stages  of  convallaria  poisoning,  the 
excitation  of  the  vagus  iu  the  neck — all 
the  branches  of  the  nerve  except  those 
going  to  heart  and  lungs  being  cut — re- 
duced the  blood-pressure  without  alter- 
ing the  frequency  of  the  beat.  Further 
researches  showed  that  the  stimulation 
of  branch  3  (Fig.  36)  even  in  unpoi- 
soned  animals  reduced  the  blood-pres- 
sure independently  of  the  variable  al- 
teration simultaneously  produced  in  the 
pulse-rate.  Stimulation  of  branch  5 
produced  an  acceleration  of  the  heart- 
beat without  increase  of  blood-pressure. 
Other  branches  brought  about  rise  of 
pressure  without  acceleration,  and  in- 
creased   discharge  by  the  left  ventricle  without  alteration   in   the  pulse-rate. 

These  results  are  supported  further  by  Wooldridge's  observation  that  exci- 
tation of  the  peripheral  ends  of  certain  nerves  on  the  posterior  surface  of  the 
ventricle  raised  the  blood-pressure  without  modifying  the  frequency  of  contrac- 
tion, and  by  Roy  and  Adami's  demonstration  that  certain  branches  of  the  first 
thoracic  ganglion  lessen  the  force  of  the  cardiac  contraction  without  influencing 
its  rhythm.        But  the  matter  is  as  yet  far  from  certain. 


Fig.  36.— Schema  of  the  centrifugal  nerves  of 
the  heart  according  to  Pawlow  :  1,  vago-sympa- 
thetic  nerve;  2,  upper  inner  branch;  3,  strong 
inner  branch;  4,  lower  inner  branch;  5,  upper 
and  lower  outer  branches;  6,  ganglion  stellatum  ; 
7,  annulus  of  Vieussens;  8,  middle  (inferior)  cer- 
vical ganglion;  9,  recurrent  laryngeal  nerve. 


The  Centripetal  Nerves  of  the  Heart. 

The  Ventricular  Nerves. — When  the  mammalian  heart  i-  freed  from 
blood  by  Avashing  it  out  with  normal  saline  solution  and  the  ventricle  Is  painted 
with  pure  carbolic  acid,  liquefied  by  warming,  numerous  nerves  appear  as 
white  threads  on  a  brown  background.  They  are  Don-medullated,  form  many 
plexuses,  and  run  beneath  the  pericardium  obliquely  downward  from  the  base 
to  the  apex  of  the  ventricle.  They  may  be  traced  to  the  cardiac  plexus. 
These  fibres  are  not  centrifugal  branches  of  the  vagus  or  the  augmentor  nerves, 
for  the  characteristic  effects  of  vagus  and  augmentor  stimulation  are  seen  after 
section  of  the  nerves  in  question.  The  stimulation  of  their  peripheral  ends, 
moreover,  the  fibre  being  carefully  dissected  out  from  the subpericardial  tis>ne, 
1liering:  Archiv fur  die gesammte  Physiologic  1894,  Ivii.  p,  78. 


172  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

cut  across,  and  the  cut  end  raised  on  a  thread  in  the  air,  is  without  effect  on 
the  blood-pressure  and  pulse-rate.  The  stimulation  of  the  central  stumps  of 
these  nerves,  <>n  the  contrary,  is  followed  by  changes  both  in  the  blood-pressure 
and  the  pulse,  showing  that  they  carry  impulses  from  the  heart  to  the  cardiac 
(•(litres  in  the  central  nervous  system,  or  perhaps,  according  to  the  views  of 
some  recent  investigators,  to  peripheral  ganglia,  thus  modifying  the  action  of 
the  heart  reflex ly. 

Sensory  Nerves  of  the  Heart. — The  stimulation  of  intracardiac  nerves 
l>y  the  application  of  acids  and  other  chemical  agents  to  the  surface  of  the 
heart  causes  various  reflex  actions,  such  as  movements  of  the  limbs.  The 
afferent  nerves  in  these  reflexes  are  the  vagi,  for  the  reflex  movements  dis- 
appear when  the  vagi  are  cut.  On  the  strength  of  these  experiments  the 
vagus  has  been  believed  to  carry  sensory  impressions  from  the  heart  to  the 
brain.  Direct  stimulation  of  the  human  heart,  in  cases  in  which  a  defect  in 
the  chest-wall  has  made  the  organ  accessible,  give  evidence  of  a  dim  and  very 
limited  recognition  of  cardiac  events — for  example,  the  compression  of  the 
heart.  Changes  in  the  force,  periodicity,  and  conduction  of  the  contraction- 
wave  may  be  produced  by  direct  electrical  stimulation  of  the  ventricle.  The 
centre  of  these  reflexes  probably  lies  in  the  bulb.1 

Vagus. — The  stimulation  of  the  central  end  of  the  cut  vagus  nerve,2  the 
other  vagus  being  intact,  causes  a  slowing  of  the  pulse-rate.  The  section  of 
the  second  vagus  causes  this  retardation  of  the  pulse  to  disappear,  indicating 
that  the  stimulation  of  the  central  end  of  the  one  affects  the  heart  reflexly 
through  the  agency  of  the  other  vagus.  The  blood-pressure  is  simultaneously 
affected,  being  sometimes  lowered  and  sometimes  raised,  the  difference  seeming 
to  depend  largely  on  the  varying  composition  of  the  vagus  in  different  ani- 
mals and  in  different  individuals  of  the  same  species.  The  stimulation  of  the 
pulmonary  branches,  by  gently  forcing  air  into  the  lungs,  loud  speaking,  singing, 
etc.,  is  said  to  increase  the  frequency  of  the  heart-beat.  Yet  the  chemical 
stimulation  of  the  mucous  membrane  of  the  lungs  is  alleged  to  slow  the  pulse- 
rate  and  lower  the  blood-pressure.  Observers  differ  as  to  the  results  of  stim- 
ulation of  the  central  end  of  the  laryngeal  branches  of  the  vagus  on  the  pulse- 
rate  and  blood-pressure. 

Depressor  Nerve. — The  earlier  stimulations  of  the  nerves  that  pass 
betweeD  the  central  nervous  system  and  the  heart,  with  the  exception  of  the 
vagus,  altered  neither  the  blood-pressure  nor  the  pulse-rate.  Ludwig  and  Cyon 
suspected  that  the  negative  results  were  owing  to  the  fact  that  the  stimulations 
were  confined  to  the  end  of  the  cut  nerve  in  connection  with  the  heart.  Some 
of  the  nerves,  they  thought,  should  carry  impulses  from  the  heart  to  the  brain, 
and  such  nerves  could  be  found  only  by  stimulation  of  the  brain  end  of  the 
cut  nerve.  They  began  their  research  for  these  afferent  nerves  with  the  branch 
which  springs  from  the  rabbit's  vagus  high  in  the  neck  and  passes  downward 
to  the  ganglion  stellatum.     Their  suspicion  was  at  once  confirmed.    The  stimu- 

1  Muskens:  Archivfur  die  gesammte  Physiologie,  1897,  lxvi.  p.  328. 
-Jlmit:  Journal  of  Physiology,  1895,  xviii.  p.  381. 


CIRCULA  TION.  1 73 

lation  of  the  central  end  of  this  nerve,  called  by  Ludwig  and  Cyon  the  depres- 
sor, caused  a  considerable  fall  of  the  blood-pressure. 

The  depressor  nerve  arises  in  the  rabbit  by  two  roots,  one  of  which  comes 
from  the  trunk  of  the  vagus  itself,  the  other  from  a  branch  of  the  vagus,  the 
superior  laryngeal  nerve.  Frequently  the  origin  is  single ;  in  that  case  it  is 
usually  from  the  nervus  laryngeus.1  The  nervus  depressor  runs  in  company 
with  the  sympathetic  nerve  to  the  chest,  where  communications  are  made  with 
the  branches  of  the  ganglion  stellatum. 

The  stimulation  of  the  peripheral  end  of  the  depressor  nerve  is  without 
effect  on  the  blood-pressure  and  heart-beat.  The  stimulation  of  the  central 
end,  on  the  contrary,  causes  a  gradual  fall  of  the  general  blood-pressure  to  the 
half  or  the  third  of  its  former  height.  After  the  stimulation  is  stopped,  the 
blood-pressure  returns  gradually  to  its  previous  level. 

Simultaneously  with  the  fall  in  blood-pressure  a  lessening  of  the  pulse-rate 
sets  in.  The  slowing  is  most  marked  at  the  beginning  of  stimulation,  and  after 
rapidly  reaching  its  maximum  gives  way  gradually  until  the  rate  is  almost 
what  it  was  before  the  stimulation  began.  After  stimulation  the  frequency  is 
commonly  greater  than  previous  to  stimulation. 

After  section  of  both  vagi,  the  stimulation  of  the  depressor  causes  no  change 
in  the  pulse-rate,  but  the  blood-pressure  falls  as  usual.  The  alteration  in  fre- 
quency is  therefore  brought  about  through  stimulation  of  the  cardiac  inhibitory 
centre,  acting  on  the  heart  through  the  vagi.  The  experiment  teaches,  further, 
that  the  alteration  in  pressure  is  not  dependent  on  the  integrity  of  the  vagi. 

Poisoning  with  curare  paralyzes  all  motor  mechanisms  except  the  heart  and 
the  muscles  of  the  blood-vessels.  Yet  curare-poisoning  does  not  affect  the 
result  of  depressor  stimulation.  The  cause  of  the  fall  in  blood-pressure  must 
be  sought  then  either  in  the  heart  or  the  reflex  dilatation  of  the  blood-vessels. 
It  cannot  be  in  the  heart,  for  depressor  stimulation  lowers  the  blood-pressure 
after  all  the  nerves  going  to  the  heart  have  been  severed.  It  must  therefore 
lie  in  the  blood-vessels.  Ludwig  and  Cyon  knew  that  the  dilatation  of 
the  intestinal  vessels  could  produce  a  great  fall  in  the  blood-pressure  and 
turned  at  once  to  them.  Section  of  the  splanchnic  nerve  caused  a  dilata- 
tion of  the  abdominal  vessels  and  a  fall  in  the  blood-pressure.  Stimula- 
tion of  the  peripheral  end  of  the  cut  splanchnic  caused  the  blood-pressure  to 
rise  even  beyond  its  former  height.  Ludwig  and  Cyon  reasoned  that  if  the 
depressor  lowers  the  blood-pressure  el. icily  by  affecting  the  splanchnic  uerve 
lvllexlv,  the  stimulation  of  the  central  end  of  the  depressor  after  section  of 
the  splanchnic  nerves  ought  to  have  little  effeel  on  the  blood-pressure.  This 
proved  to  be  the  case.  The  investigators  concluded  thai  the  depressor  re- 
duces the  blood-pressure  chiefly  by  lessening  the  tonus  of  the  vessels  governed 
by  the  splanchnic  nerve,  thus  allowing  their  dilatation  and  in  consequence 
lessening  the  peripheral  resistance.  The  fallacy  in  this  argument  has  re- 
cently been  pointed  out  l>v  Porter  and  Beyer.2     The  stimulation  of  the  >\<'- 

1  Tseliirwinsky :  Centralblatt  fur  Physiologie,  1896,  i\.  \<  778,  gives  :>  somewhat  different 
account. 

*  Porter  and  Beyer:   American  Journal  of  Physiology,  L900,  \\iii. 


174 


AN   AMERICAN    TEXT- BO  OK    OF   PHYSIOLOGY. 


pressor  after  .section  of  the  splanchnic  nerves  has  little  effect,  because  the 
blood-pressure  is  already  so  low  when  the  stimulation  is  made  that  it  can  sink 
but  little  more.  When,  however,  the  pressure  is  restored  to  its  normal  level, 
alter  section  of  the  splanchnic  nerve-  by  the  stimulation  of  their  peripheral 
ends,  or  by  the  injection  of  normal  saline;  solution  into  the  vessels  and  the 
depressors  then  stimulated,  the  fall  in  blood-pressure  is  nearly  and  some- 
times quite  as  great  as  that  obtained  by  the  stimulation  of  the  depressor 
nerve  when  the  splanchnic  nerves  are  intact.  Jt  is  improbable,  therefore, 
that  the  depressor  acts  chiefly  through  the  splanchnic  nerves.  It  probably 
acts  mi  all  the  vasomotor  nerves  connected  with  the  vasomotor  centre.  This 
view  is  somewhat  strengthened  by  the  observations  of  Bayliss  (Fig.  37). 

It  has  already  been  said  that  the  depressor  fibres  pass  from  the  heart  to  the 
vaso-motor  mechanism  in  the  central  nervous  system.  The  cardiac  fibres  are 
probably  stimulated  when  the  heart  is  overfilled  through  lack  of  expulsive 
force  or  through  excessive  venous  inflow,  and,  by  reducing  the  peripheral  resist- 
ance, assist  the  engorged  organ  to  empty  itself. 

The  depressor  nerve  is  not  in  continual  action  ;  it  has  no  tonus;  for  the  sec- 
tion of  both  depressor  nerves  causes  no  alteration  in  the  blood-pressure. 

Sewall  and  Steiner  have  obtained  in  some  cases  a  permanent  rise  in  blood- 
pressure  following  section  of  both  depressors,  yet  they  hesitate  to  say  that  the 
depressor  exercises  a  tonic  action. 

Spallita  and  Consiglio    have  stimulated  the  depressor  before  and  after  the 


Fig.  37.— Showing  the  fall  in  blood-pressure  and  the  dilatation  of  peripheral  vessels  from  stimula- 
tion of  the  central  end  of  the  depressor  nerve  i  Bayliss) :  A,  curve  of  blood-pressure  in  the  carotid  artery  ; 
B,  volume  of  hind  limb,  recorded  by  a  plethysmograph ;  (7,  electro-magnet  lino,  in  which  the  elevation 
the  time  of  stimulation  of  the  nerve ;  D,  atmospheric  pressure-line ;  E,  time  in  seconds. 

section   of  the  spinal  accessory  nerve  near  its  junction  with  the  vagus.     They 

find  that  after  section  of  the  spinal  accessory,  the  stimulation  of  the  depressor 

does  not  affect  the  pulse,  whence  they  conclude  that  the  depressor  fibres  that 

affect  the  blood-pressure  are  separate  from  those  that  affect  the  rate  of  beat,  the 

latter  being  derived  from  the  spinal  accessory  nerve. 

A  recent  study  by  Bayliss1  brings  out  several  new  facts.    If  a  limb  is  placed 

1  Bayliss:  .J<»inxtl  of  Physiology,  1893,  xiv.  p.  303.     The  relation   between  the  depressor 
nerve  and  the  thyroid  i-  pointed  nut  by  v.  ( 'von  :  ( '  ,.-   •  .'  \ttfur  Physiologic,  1897,  ii.  pp.  279,  357. 


CIRCULA  TION.  1  7  5 

in  Mosso's  plethysmograph  and  the  central  end  of  the  depressor  stimulated, 
the  volume  of  the  limb  increases,  showing  an  active  dilatation  of  the  vessels 
that  supply  it.  The  latent  period  of  this  dilatation  varies  greatly.  The  vessels 
of  the  skin  play  a  large  part  in  its  production.  A  similar  local  action  is  seen 
on  the  vessels  of  the  head  and  neck  (see  Fig.  37). 

The  depressor  fibres  vary  much  in  size  in  different  animals.  When  the 
nerve  is  small,  a  greater  depressor  effect  can  be  obtained  by  stimulating  the 
central  end  of  the  vagus  than  from  the  depressor  itself.  But  the  course  of  the 
fall  is  different  in  the  two  cases.  With  the  depressor,  the  fall  is  maintained  at 
a  constant  level  during  the  whole  excitation,  however  long  it  lasts,  whereas 
in  the  case  of  the  vagus  the  pressure  very  soon  returns  to  its  original 
height  although  the  excitation  still  continues.  Bayliss  believes,  therefore, 
that  there  is  a  considerable  difference  between  the  central  connections  of  the 
depressor  nerve  itself  and  the  depressor  fibres  sometimes  found  in  other  nerves. 

The  left  depressor  nerve  usually  produces  a  greater  fall  of  pressure  than  the 
right.  The  excitation  of  the  second  nerve  dui'ing  the  excitation  of  the  first 
produces  a  greater  fall  than  the  excitation  of  one  alone. 

The  fibres  of  the  depressor,  in  part  at  least,  end  in  the  wall  of  the  ventricle. 
A  similar  nerve  has  been  demonstrated  in  the  cat,  horse,  dog,  sheep,  swine, 
and  in  man. 

Sensory  Nerves. — The  first  and  usually  the  only  effect  of  the  stimulation 
of  the  central  end  of  a  mixed  nerve  like  the  sciatic,  according  to  Roy  and 
Adami,  is  an  increase  in  the  force  and  the  frequency  of  the  heart-beat.  Other 
observers  have  sometimes  found  quickening  and  sometimes  slowing  of  the  pulse- 
rate,  so  that  sensory  nerves,  as  Tigerstedt  suggests,  appear  to  affect  both  the 
inhibitory  and  the  augmenting  heart-nerves.  When  a  sensory  nerve  is  weakly 
excited  the  augmentor  effect  predominates,  when  strongly  excited  the  inhibi- 
tory. A  well-known  demonstration  of  the  reflex  action  of  the  sensory  nerves 
on  the  heart  is  seen  in  the  slowing  of  the  rabbit's  heart  when  the  animal 
is  made  to  inhale  chloroform.  The  superior  laryngeal  and  the  trigeminus 
nerves,  especially  the  latter,  convey  the  stimulus  to  the  nerve-centres. 

The  stimulation  of  t he  nerves  of  special  sense,  optic,  auditory,  olfactory  and 
glosso-pharyngeal  nerves,  also  sometimes  slows  and  sometimes  quickens  the 
heart. 

Sympathetic. — The  reflex  action  of  the  sympathetic  nerve  upon  the  heart 
is  well  shown  by  the  celebrated  experiment  of  F.  Goltz.  In  a  medium-sized 
frog,  the  pericardium  was  exposed  by  carefully  cutting  a  small  window  in  the 
chest-wall.  The  pulsations  of  the  heart  could  be  seen  through  the  thin  peri- 
cardial membrane.  Goltz  now  began  to  heat  upon  the  abdomen  aboul  1  10 
times  a  minute  witli  the  handle  of  a  scalpel.  The  heart  gradually  slowed,  and 
at  length  stood  still  in  diastole.  Goltz  now  ceased  the  rain  of  little  blows. 
The  heart  remained  quiet  for  a  time  and  then  began  to  beat  again.  ;it  firsl  slowly 
and  then  more  rapidly.  Some  time  after  the  experiment,  the  heart  beal  about 
five  strokes  in  the  minute  faster  than  before  the  experiment  was  begun.  The 
effect  cannot  be  obtained  after  section  of  the  vaffi. 


176  AN  AMERICAN    TEXT-HOOK    OF    PHYSIOLOGY. 

Bernstein  found  that  the  afferent  nerves  in  Goltz's  experiment  were  branches 
of  the  abdominal  sympathetic,  and  discovered  that  the  stimulation  of  the  cen- 
tral end  of  the  abdominal  sympathetic  in  the  rabbit  was  followed  also  by  reflex 
inhibition  of  the  heart. 

The  stimulation  of  the  central  end  of  the  splanchnic  produces  a  reflex  rise 
of  blood-pressure  and,  perhaps  secondarily,  a  slowing  of  the  heart.  In  some 
cases  acceleration  has  been  observed.  According  to  Roy  and  Adami  splanch- 
nic stimulation  sometimes  produces  a  combination  of  augmentor  and  vagus 
effects,  the  augmentation  appearing  during  stimulation  and  giving  place 
abruptly  to  well-marked   inhibitory  slowing  at  the  close  of  stimulation. 

The  results  of  stimulating  various  abdominal  viscera  have  been  studied  by 
Mayer  and  Pribram.  One  of  the  most  interesting  of  the  reflexes  observed  by 
them  was  the  inhibition  of  the  heart  called  forth  by  dilating  the  stomach. 

The  stimulation  of  the  cervical  sympathetic  does  not  give  any  very  constant 
results  on  the  action  of  the  heart. 

B.  The  Centres  op  the  Heart-nerves. 

Inhibitory  Centre. — It  has  been  already  mentioned  that  the  brothers 
Weber  localized  the  cardiac  inhibitory  centre  in  the  medulla  oblongata.  The 
efforts  to  fix  the  exact  location  of  the  centre  by  stimulation  of  various  parts, 
either  mechanically,  by  thrusting  fine  needles  into  the  medulla,  or  electrically, 
cannot  inspire  great  confidence  because  of  the  difficulty  of  distinguishing 
between  the  results  that  follow  the  excitation  of  a  nerve-path  from  or  to  the 
centre  and  those  following  the  excitation  of  the  centre  itself.  According  to 
Laborde,  who  also  used  this  method,  the  cardiac  inhibitory  centre  is  situated  at 
the  level  of  the  mass  of  cells  known  as  the  accessory  nucleus  of  the  hypoglossus 
and  the  mixed   nerves  (vagus,  spinal  accessory,  glosso-pharyngeal). 

The  localization  of  the  centre  by  the  method  of  successive  sections  is  per- 
haps more  trustworthy.  Franck  has  found  that  the  separation  of  the  bulb 
from  the  spinal  cord  cuts  off  the  reflexes  called  forth  by  nerves  that  enter  the 
spinal  cord,  while  leaving  undisturbed  the  reflex  produced  by  stimulation  of 
the  trigeminus  nerve. 

On  the  whole,  there  seems  to  be  no  doubt  that  the  cardiac  inhibitory  centre 
is  situated  in  the  bulb. 

Tonus  of  Card/in-  Inhibitory  Centre. — The  cardiac  inhibitory  centre  is  prob- 
ably always  in  action,  for  when  the  vagus  nerves  are  cut,  the  heart-beat 
becomes  more  frequent.1  The  source  of  this  continued  or  "tonic"  activity 
may  lie  in  the  continuous  discharge  of  inhibitory  impulses  created  by  the 
liberation  of  energy  in  the  cell  independent  of  direct  external  influences,  or 
the  cells  may  be  discharged  by  the  continuous  stream  of  afferent  impulses 
that  must  constantly  play  upon  them  from  the  multitude  of  afferent  nerves. 
This  latter  theory,  the  conception  of  a  reflex  tonus,  is  made  probable  by  the 
observations  that  section  of  the  vagi  docs  not  increase  the  rate  of  beat  after 
the  greater  part  of  the  afferent  impulses  have  been  cul  oil*  by  division  of  the 
1  Hunt  :  American  Journal  oj  Physiology,  1899,  ii.  p.  397. 


CIRCULATION.  177 

spinal  cord  near  its  junction  with  the  bulb,  and  that  the  sudden  decrease  in 
the  number  of  afferent  impulses  caused  by  section  of  the  splanchnic  nerve 
quickens  the  pulse-rate. 

Irradiation. — The  slowing  of  the  rate  of  beat  observed  chiefly  during  the 
expiratory  portion  of  respiration  disappears  after  the  section  of  both  vagus 
nerves.  The  slowing  may  perhaps  be  due  to  the  stimulation  of  the  cardiac 
inhibitory  centre  by  irradiation  from  the  respiratory  centre.1 

Origin  of  Cardiac  Inhibitory  Fibres. — Since  the  researches  of  Waller  and 
others,  it  has  been  generally  believed  that  the  cardiac  inhibitory  fibres  enter 
the  vagus  from  the  spinal  accessory  nerve,  for  the  reason  that  cardiac  inhibi- 
tion was  not  secured  in  animals  in  which  the  fibres  in  the  vagus  derived  from 
the  spinal  accessory  nerve  were  made  to  degenerate  by  tearing  out  the  latter 
before  its  junction  with  the  vagus.  These  results  have  lately  been  called  in 
question  by  Grossmann.2  The  method  employed  by  his  predecessors,  according 
to  him,  probably  involved  the  destruction  of  vagus  roots  as  well  as  those  of 
the  spinal  accessory.  Grossmann  finds  that  the  stimulation  of  the  spinal 
accessory  nerve  before  its  junction  with  the  vagus  does  not  inhibit  the  heart. 
Nor  does  inhibition  follow  the  stimulation  of  the  bulbar  roots  supposed  to  be 
contributed  to  the  mixed  nerve  by  the  spinal  accessory. 

Augmentor  Centre. — The  situation  of  the  centre  for  the  augmentor 
nerves  of  the  heart  is  not  definitely  known,  although  from  analogy  it  seems 
probable  that  it  will  be  found  in  the  bulb.  That  this  centre  is  constantly  in 
action  is  indicated  by  the  lowering  of  the  pulse-rate  after  section  of  the  vagi 
followed  by  the  bilateral  extirpation  of  the  inferior  cervical  and  first  thoracic 
ganglia.3  The  division  of  the  spinal  cord  in  the  upper  cervical  region  after  the 
section  of  the  vagi  has  the  same  effect.  Vagus  inhibition,  moreover,  is  said 
to  be  more  readily  produced  after  section  of  the  augmentor  nerves. 

McWilliam  '  has  remarked  that  the  latent  period  and  the  character  of  the 
acceleration  often  accompanying  the  excitation  of  afferent  nerves  may  differ 
entirely  from  the  characteristic  effects  of  the  excitation  (if  augmentor  nerves. 
The  stimulation  of  the  latter  is  followed  by  a  long  latent  period,  after  which 
the  rate  of  beat  gradually  increases  to  its  maximum  and,  after  excitation  is 
over,  as  gradually  declines.  The  excitation  of  an  afferent  nerve,  on  the  con- 
trary, causes  often,  with  almost  no  latent  period,  a  remarkably  sudden  accel- 
eration, that  reaches  at  once  a  high  value  and  often  suddenly  gives  way  to  a 
slow  heart-beat.  These  facts  seem  to  show  that  reflex  acceleration  of  the  heart- 
beat is  due  to  chaDges  in  the  cardiac  inhibitory  centre,  and  not  to  augmentor 
excitation.  This  view  is  strengthened  by  the  fad  that  if  the  augmentor  nerve- 
are  cut,  the  vagi  remaining  intact,  the  stimulation  of  afferent  fibres,  for  exam- 
ple in  the  brachial  nerves,  can  still  cause  a  marked  quickening  of  the  pulse- 
rate.     In  short,  the  action  of  afferent  nerves  upon  the  rateofbeal  is  essentially 

LLaulani£:  Comptes  rendus  Soci&i  de  Biologie,  1893,  p.  ~'2'.\.     Compare  Wood:    American 

Journal  of  I'/iiisi<>h,,/,i,  Is'.i'.i,  ii.  p.  :>.VJ. 

'  <  rrossmann  :  Archiv  fur  die  gesammte  Physiologic,  1895,  liv.  p.  6 
3  Hunt:    Amrrirun  Jniirwtl  <>f   /'//i/.si'o/of/;/,  IS",)',),  ii.  p.  397. 
*  McWilliam  :  Proceedings  Royal  Society,  L893,  liii.  p.  I7"_\ 

Vol.  1.— 12 


ITS  AJS   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

the  same,  according  to  this  observer,  whether  the  augmentor  nerves  are  divided 
or  intact. 

Roy  and  Adami  believe  that  the  stimulation  of  afferent  nerves,  such  as  the 
sciatic  or  the  splanchnic,  excites  both  augmentor  and  vagus  centres.  The 
augmentor  centre  is  almost  always  the  more  strongly  excited  of  the  two,  so 
that  augmentor  effects  alone  are  usually  obtained. 

Action  of  Higher  Parts  of  the  Brain  on  Cardiac  Centres. — Repeated 
efforts  have  been  made  to  find  areas  in  the  cortex  of  the  brain  especially 
related  to  the  inhibition  or  augmentation  of  the  heart,  but  with  results  so  con- 
tradictory  as  to  warrant  the  conclusion  that  the  influence  on  the  heart-beat 
of  the  parts  of  the  brain  lying  above  the  cardiac  centres  does  not  differ  essen- 
tially from  that  of  other  organs  peripheral  to  those  centres. 

Voluntary  control  of  the  heart,  by  which  is  meant  the  power  to  alter  the 
rate  of  beat  by  the  exercise  of  the  will,  is  impossible  except  as  a  rare  indi- 
vidual peculiarity,  commonly  accompanied  by  an  unusual  control  over  muscles, 
such  as  the  platysma,  not  usually  subject  to  the  will.  Cases  are  described  by 
Tarchanoff  and  Pease,  in  which  acceleration  of  the  beat  up  to  twenty-seven 
in  the  minute  was  produced,  together  with  increase  of  blood-pressure,  from 
vaso-constrictor  action.     The  experiments  are  dangerous.1 

Peripheral  Reflex  Centres. — It  is  now  much  discussed  whether  the  periph- 
eral ganglia  can  act  as  centres  of  reflex  action.  According  to  Franck2  the  excita- 
tion of  the  central  stump  of  the  divided  left  anterior  limb  of  the  annulus  of 
Vieussens  is  transformed  within  the  first  thoracic  ganglion,  isolated  from  the 
spinal  cord  by  section  of  its  rami  communicantes,  into  a  motor  impulse  trans- 
mitted by  the  posterior  limb  of  the  annulus.  This  motor  impulse  causes,  inde- 
pendently of  the  bulbo-spinal  centres,  a  reflex  augmentation  in  the  action  of  the 
heart,  and  a  reflex  constriction  of  the  vessels  in  the  external  ear,  the  submaxil- 
lary gland,  and  the  nasal  mucous  membrane.  This  experiment,  in  conjunction 
with  the  tacts  in  favor  of  other  sympathetic  ganglia  acting  as  reflex  centres/ 
seems  to  demonstrate  that  some  afferent  impulses  are  transformed  in  the  sym- 
pathetic cardiac  ganglia  into  efferent  impulses  modifying  the  action  of  the 
heart.  It'  this  conclusion  is  confirmed  by  future  investigations  it  will  pro- 
foundly modify  the  views  now  entertained  regarding  the  innervation  of  the 
heart. 

The  exp&irnenU  of  Stannius,  published  in  1852,  have  been  the  starting- 
point  of  a  very  -rent  number  of  researches  on  the  innervation  of  the  frog's 
heart.  Stannius  observed,  among  other  facts,  that  the  heart  remained  for  a 
time  arrested  in  diastole  when  a  ligature  was  tied  about  the  heart  precisely  at 
the  junction  of  the  sinus  venosus  with  the  right  auricle.  No  sufficient 
explanation  of  this  result  has  yet  been  given,  nor  is  one  likely  to  be  found 
until  the  innervation  of  the    heart    is   better    understood.     Stannius     further 

1  Van  de  Velde  :  Archivfur  die  gesammte  Physiologic,  1897,  lxvi.  p.  232. 

2  Franck  :  Archives  de  Physiologic,  1894,  p.  721. 

3  Langley  and  Anderson  :  Journal  of  Physiology,  1894,  xvi.  p.  435.  The  attempt  of  Prof. 
Kxonecker  to  demonstrate  a  co-ordinating  centre  in  the  ventricles  may  be  mentioned  here  (Zeit- 
schrift  fur  Biolagie,  1896,  xxxiv.  p  529). 


CIRCULATION.  17;) 

observed  that  after  the  ligature  just  described  had  been  drawn  tight,  thus 
arresting  the  heart,  the  placing  of  a  second  ligature  around  the  heart  at  the 
junction  of  the  auricle  and  ventricle  caused  the  latter  to  begin  to  beat  again, 
while  the  auricle  remained  at  rest.  This  second  ligature,  it  is  generally 
admitted,  stimulates  the  ganglion  of  Bidder,  and  the  ventricle  responds  by 
rhythmic  contractions  to  the  constant  excitation  thus  produced.  Loosening  the 
ligature  and  so  interrupting  the  excitation  stops  the  ventricular  beat. 


PART   III.— THE   NUTRITION   OF   THE    HEART. 

The  cells  of  which  the  heart-wall  are  composed  are  nourished  by  contact 
with  a  nutrient  fluid.  In  hearts  consisting  of  relatively  few  cells  no  special 
means  of  bringing  the  nutrient  fluid  to  the  cells  is  required.  The  walls  of  the 
minute  globular  heart  of  the  small  crustacean  Daphnia,  for  example,  arc  com- 
posed of  a  single  layer  of  cells,  each  of  which  is  bathed  by  the  fluid  which  the 
heart  pumps.  In  larger  hearts  with  thicker  walls  only  the  innermost  cells 
could  be  fed  in  this  way.  Special  means  of  distributing  the  blood  throughout 
the  substance  of  the  organ  are  necessary  here. 

Passages  in  the  Prog's  Heart. — In  the  frog  this  distribution  is  accom- 
plished chiefly  through  the  irregular  passages  which  go  out  from  the  cavities 
of  the  heart  between  the  muscle-bundles  to  within  even  the  fraction  of  a  milli- 
meter of  the  external  surface.  These  passages  vary  greatly  in  size.  Many  arc 
mere  capillaries.  They  are  lined  by  a  prolongation  of  the  endothelium  of  the 
heart.  Filled  by  every  diastole  and  emptied  by  every  systole,  they  do  the 
work  of  blood-vessels  and  carry  the  blood  to  every  part  of  the  cardiac  muscle. 
Henri  Martin  !  describes  a  coronary  artery  in  the  frog,  analogous  to  the 
coronary  arteries  of  higher  vertebrates.  This  artery  supplies  a  part  of  the 
auricles  and  the  upper  fourth  of  the  ventricle. 

In  the  rabbit,  cat  and  dog,  and  in  man  a  well-developed  system  of  cardiac 
vessels  exists,  the  coronary  arteries  and  veins.  Their  distribution  in  the  dog 
deserves  especial  notice,  because  the  physiological  problems  connected  with  these 
vessels  have  been  studied  chiefly  in  this  animal. 

Coronary  Arteries  in  the  Dog. —  In  the  dog  the  coronary  arteries  and 
their  larger  branches  lie  upon  the  surface  of  the  heart,  covered  as  a  rule  only 
by  the  pericardium  and  a  varying  quantity  of  connective  tissue  and  fat.  The 
left  coronary  artery  is  extraordinarily  short.  A  few  millimeters  after  its  origin 
from  the  aorta  it  divides  into  the  large  ramus  circumflex  and  the  descen- 
dens,  nearly  as  large.  The  former  runs  in  the  auriculo-ventricular  furrow 
around  the  left  side  of  the  heart  to  the  posterior  surface,  ending  in  the  pos- 
terior inter-ventricular  furrow.  The  left  auricle  and  the  upper  anterior  and  the 
posterior  portion  of  the  left  ventricle  arc  supplied  by  this  artery.  The  descen- 
dens  runs  downward  in  the  anterior  inter-ventricular  furrow  to  the  apex.  (  Hose 
to  its  origin  the  descendens  gives  oil"  the  artcria  septi,  which   al  once  enter-  the 

'Martin  :   Comptes  rendus  Socteti  de  Biologie,  1893,  p.  754, 


180  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

inter-ventricular  septum  and  passes,  sparsely  covered  with  muscle-bundles, 
obliquely  downward  and  backward  on  the  right  side  of  the  septum.  The 
descendens  in  its  farther  course  gives  off  numerous  branches  to  the  left  ventricle 
and  the  anterior  part  of  the  septum.  Only  a  few  small  branches  go  to  the 
right  ventricle.  Thus  the  descendens  supplies  the  septum  and  the  inferior 
anterior  pari  of  the  left  ventricle.  The  right  coronary  artery,  imbedded  in 
fat,  runs  in  the  right  auriculo-ventricular  groove  around  the  right  side  of  the 
heart,  supplying  the  right  auricle  and  ventricle.  It  is  a  much  smaller  artery 
than  either  the  circumflex  or  descendens.  Each  coronary  artery  keeps  to  its 
own  boundaries  and  does  not,  in  the  dog,  pass  into  the  field  of  another  artery, 
:i~  sometimes  happens  in  man.1 

Terminal  Nature  of  Coronary  Arteries. — The  coronary  arteries  in  the 
dog,  as  in  man,  are  terminal  arteries,  that  is,  the  anastomoses  which  their  branches 
have  with  neighboring  vessels  do  not  permit  the  making  of  a  collateral  circula- 
tion. Their  terminal  nature  in  the  human  heart  is  shown  by  the  formation  of 
infarcts  in  the  areas  supplied  by  arteries  which  have  been  plugged  by  embo- 
lism or  thrombosis.  That  part  of  the  heart-wall  supplied  by  the  stopped  artery 
speedily  decays.  The  bloodless  area  is  of  a  dull  white  color,  often  faintly 
tinged  with  yellow  ;  rarely  it  is  red,  being  stained  by  haemoglobin  from  the 
neighboring  capillaries.  The  cross  section  is  coarsely  granular.  The  nuclei 
of  the  muscle-cells  have  lost  their  power  of  staining.  The  muscle-cells  are 
dead  and  connective  tissue  soon  replaces  them.-  This  loss  of  function  ami 
rapid  decay  of  cardiac  tissue  would  not  take  place  did  anastomoses  permit  the 
establishment  of  collateral  circulation  between  the  artery  going  to  the  part  and 
neighboring  arteries.  The  terminal  nature  of  the  coronary  arteries  in  the  dog 
has  been  placed  beyond  doubt  by  direct  experiment.  It  is  possible  to  tie  them 
and  keep  the  animal  alive  until  a  distinct  infarct  has  formed.3 

The  objection  that  one  of  the  coronary  arteries  can  be  injected  from 
another,4  and  that  therefore  they  are  not  terminal,  is  based  on  the  incorrect 
premise  that  terminal  arteries  cannot  be  thus  injected,  and  has  no  weight  against 
the  positive  evidence  of  the  complete  failure  of  nutrition  following  closure. 
The  passage  of  a  fine  injection-mass  from  one  vascular  area  to  another  proves 
nothing  concerning  the  possibility  of  the  one  area  receiving  its  blood-supply 
from  the  other.  Such  supply  is  impossible  if  the  resistance  in  the  communi- 
cating vessels  i-  greater  than  the  blood-pressure  in  the  smallest  branches  of  the 
arterv  through  which  the  supply  imi-i  come,  it  is  the  fact  of  this  high  resist- 
ance, due  to  the  small  size  of  the  communicating  branches,  which   makes  the 

artery  ••terminal."     This  c lit  ion  of  high  resistance  is  really  present  during 

life,  or  infarction  could  not  take  place. 

The  terminal   nature  of  the  coronary  arteries   is   of  great    importance  with 

regard  to  the  part  taken   by  them    in   the  nutrition  of  the  heart.      Being  ter- 

1  Baumgarten  :  American  Journal  oj   Physiology,  1899,  ii.  p.  243. 

also  the  description  by  Kolster:  Skandinavisches  Archiv  fur  Physiologie,  1893,  iv.  p. 
14,  of  the  infarctions  produced  experimentally  in  t lie  il"-'-  heart. 
Porter:   Archiv fiir  du  gt  ammt    Physiologie,  1893,  lv.  p.  366. 
4  Michaelis :  Zeitschrifl  fur  klinische  Medicin,  1894,  xxiv.  p.  289. 


CIRCULATION.  181 

minal,  their  experimental  closure  enables  us  to  study  the  effects  of  the  sudden 
stopping  of  the  blood-supply  (ischsemia)  of  the  heart  muscle  upon  the  action 
of  the  heart. 

Results  of  Closure  of  the  Coronary  Arteries. — The  sudden  closure  of  one 
of  the  large  coronary  branches  in  the  dog  has  as  a  rule  cither  no  effect  upon 
the  action  of  the  heart  beyond  occasional  and  transient  irregularity,1  or  is  fol- 
lowed after  the  lapse  of  seconds,  or  of  minutes,  by  the  arrest  of  the  ventricu- 
lar stroke,  the   ventricle  falling  a   moment   later  into   the   rapid,  fluttering, 


Fig.  'S8.—A,  curve  of  intraventricular  pressure,  written  by  a  manometer  connected  with  the  interior 
of  the  left  ventricle;  B,  atmospheric  pressure;  C,  time  in  two-second  intervals.  At  the  first  arrow  the 
ramus  circumflexus  of  the  left  coronary  artery  was  ligated ;  at  the  second  arrow  the  hear!  fell  Into  fibril- 
lary contractions.  The  lessening  height  of  the  curve  shows  the  gradual  diminution  of  the  force  of  con- 
traction after  ligation.  The  rise  of  the  lower  line  of  the  curve  above  the  atmospheric  pressure  indicates 
a  rise  of  intra-ventricular  pressure  during  diastole.  The  small  elevations  in  the  pressure-curve  after  the 
second  arrow  are  caused  by  the  left  auricle,  which  continued  to  beat  after  the  arrest  of  the  ventricle 
(Porter,  1893). 

undulatory  movements  known  as  fibrillary  contractions  and  produced  by  the 
inco-ordinated,  confused  shortenings  of  individual  muscle-cells,  or  groups  of 
cells.  The  auricles  continue  to  beat  for  a  time,  but  the  power  of  the  ventricles 
to  execute  co-ordinated  contractions  is  lost. 

The  Frequency  of  Arrest. — The  frequency  with  which  closure  is  fol- 
lowed by  ventricular  arrest  depends  on  at  least  two  factors — namely,  the  size 
of  the  artery  ligated  and  the  irritability  of  the  heart.  That  the  size  of  the 
artery  is  of  influence  appears  from  a  series  of  ligations  performed  on  dogs, 
arrest  being  never  observed  after  ligation  of  the  arteria  septi  alone,  rarely 
observed  (14  per  cent.)  with  the  right  coronary  artery,  more  frequently  (28 
per  cent.)  with  the  descendens,  and  still  more  frequently  (80  per  cent.)  with  the 
arteria  circumflexa.2  The  irritability  of  the  heart  is  an  important  factor.  In 
animals  cooled  by  long  artificial  respiration,  or  by  section  of  the  spinal  cord  at 
its  junction  with  the  bulb,  the  ligation  of  the  descendens  arrests  the  hearl  less 
frequently  than  in  vigorous  animals  which  have  been  operated  upon  quickly. 
The  frequency  of  arrest  is  increased  by  the  use  of  morphia  and  curare/' 

Changes  in  the  Heart-beat. —  Ligation  destined  to  arrest  the  heart  i-  fol- 
lowed almost  immediately  by  a  continuous  fall  in  the  intra-ventricular  pressure 
during  systole  and  a  gradual  rise  in  the  pressure  during  diastole  (see  Fig.  38). 
The  contraction  and  relaxation  of  the  ventricle  are  often  slowed.  The  force 
of  the  ventricular  stroke  is  diminished.  As  arrest  draw-  near,  irregularities  in 
the  force  of  the  ventricular  beat  are  seldom  absent.  The  frequency  of  beat  is 
sometimes  unchanged  throughout,  but    is  usually  diminished  toward  the  end j 

1  The  changes  produced  by  subsequent  degeneration  are  1 1  <  •  t  considered  bere. 
*  Porter:  Journal  of  Physiology,  1893,  sv.  p.  131. 
8Porter:  Journal  of  Experimented  Medicine,  1896,  i,  p.  49. 


182 


AX  AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY 


Fig.  39.— Showing  fall  in  arte- 
rial pressure  and  diminished  out- 
put of  left  ventricle  inconsequence 
of  the  ligation  "f  the  circumflex 
artery.  'I  he  curve  reads  from  left 
to  right,  it  isone-balf  the  original 
I  In-  upper  curve  is  the  pres- 
sure in  the  carotid  artery.  The 
unbroken  line  is  atmospheric  pres- 
sure. The  next  curve  is  the  na 
nremenl  >>i  the  outflow  from  the 
left  ventricle,  each  rise  and  each 
fall  indicating  the  passage  of  50 

c.cm.  of  bl l  i  ii  t  •  >  the  aorta      i  he 

lower  line  is  a  time-curve  in  sec- 
onds. At  *  the  circumflex  artery 
was  ligated  (Porter,  L896,  p.  51). 


occasionally  the  frequency  is  increased.  Both  ven- 
tricles as  a  rule  cease  to  heat  at  the  same  instant. 
The  work  done  hy  the  heart,  measured  by  the 
blood  thrown  into  the  aorta  in  a  unit  of  time,  is 
lessened  by  ligation  when  followed  by  arrest  (see 
Fig.  39). 

The  Exciting'  Cause  of  Arrest. — There  are 
two  opinions  concerning  the  exciting  cause  of  the 
changes  following  closure  of  a  coronary  artery, 
some  investigators  holding  for  anaemia  and  others 
for  mechanical  injury  of  the  cardiac  muscle  or  its 
nerves  in  the  operation  of  ligation.  The  latter 
base  their  claim  on  the  frequent  failure  of  ligation 
of  even  a  main  branch  to  stop  the  heart;  on  the 
fact  that  the  heart  of  the  dog  has  been  seen  to 
beat  from  115  to  150  seconds  after  the  blood-pres- 
sure in  the  aorta  was  so  far  reduced,  by  clamping 
the  auricle  and  opening  the  carotid  artery,  as  to 
make  a  continuance  of  the  coronary  circulation 
very  improbable;1  on  the  revival  of  the  arrested 
heart  by  the  injection  of  defibriuated  blood  into 
the  coronary  arteries  from  the  aorta,  by  which 
means  the  dog's  heart  and  even  the  human  heart 
has  been  made  to  beat  again  many  minutes  after 
the  total  arrest  of  the  circulation,2 — it  being  as- 
sumed, incorrectly,  that  the  dog's  heart  cannot  be 
made  to  beat  after  arrest  with  fibrillary  contrac- 
tions; and,  finally,  on  the  arrest  with  fibrillary 
contractions  which  some  experimenters  have  caused 
by  mechanical  injury  to  the  heart. 

To  sum  up,  the  argument  in  favor  of  explain- 
ing arrest  with  fibrillary  contractions  simply  by 
the  mechanical  injury  done  the  heart  in  the  pro- 
cess of  ligation  consists  of  two  propositions :  first, 
anemia  without  mechanical  injury  does  not  cause; 
arrest  with  fibrillary  contractions;  and  second,  me- 
chanical injury  without  anemia  does  cause  arrest. 

Against  the  second  of  these  propositions  must 
be  placed  the  extreme  infrequency  of  arrest  from 
mechanical  injuries."'      In  more  than  one  hundred 

1  Tigerstedt :  Skandinavischea  Archiv  fiir  Physiologie,  1S93, 
v.  p.  71  ;  Michaelis  :  Zeitschrifl  fin-  klinisehe  Medicin,  1894, 
xxiv.  p.  'J7<>. 

-  Langendorff:  Archiv  fiir  die  gesammte  Physiologie,  L895, 
].\i.  p.  320;  1898,  Ixx.  p.  281 ;  Batke:  Ibid.,  1898,  Ixxi.  p.  412. 

:;  Rodel  ami  Nicolas:  Archives de  Physiologie,  1896,  p.  167. 


CIRCULA  TJOJY.  1 83 

ligations  Porter  observed  not  a  single  arrest  in  consequence  of  laying  the 
artery  bare  and  placing  the  ligature  ready  to  be  drawn,  the  only  effect  of  the 
mechanical  procedure  being  an  occasional  slight  irregularity  in  force.  Ligation 
of  the  periarterial  tissues  in  ten  dogs,  the  artery  itself  being  excluded  from  the 
ligature,  directly  injured  both  muscular  and  nervous  substance,  but  was  only 
once  followed  by  arrest.  Nor  does  arrest  follow  the  ligation  of  a  vein,  although 
the  mechanical  injury  is  possibly  as  great  as  in  tying  an  artery.  The  direct 
stimulation  of  the  superficial  ventricular  nerves  exposed  to  injury  in  the  opera- 
tion of  ligation  does  not  produce  the  effects  that  appear  after  the  ligation  of 
coronary  arteries. 

Against  the  remaining  proposition  stated  above — namely,  that  anaemia  with- 
out mechanical  injury  does  not  cause  arrest  with  fibrillary  contractions — it 
should  be  said  that  the  frequency  of  arrest  after  ligation  is  in  proportion  to 
the  size  of  the  artery  ligated,  and  hence  to  the  size  of  the  area  made  anaemic, 
and  is  not  in  proportion  to  the  injury  done  in  the  preparation  of  the  artery. 
The  circumflex  and  descendens  may  be  prepared  without  injuring  a  single 
muscle-fibre,  yet  their  ligation  frequently  arrests  the  heart,  while  the  ligation 
of  the  arteria  septi,  which  cannot  be  prepared  without  injuring  the  muscle- 
substance,  does  not  arrest  the  heart.  It  is,  moreover,  possible  to  close  a  coro- 
nary artery  without  mechanical  injury.  Lycopodium  spores  mixed  with  de- 
fibrinated  blood  are  injected  into  the  arch  of  the  aorta  during  the  momentary 
closure  of  that  vessel  and  are  carried  into  the  coronary  arteries,  the  only  way 
left  open  for  the  blood.  The  lycopodium  spores  plug  up  the  finer  branches 
of  the  coronary  vessels.  The  coronary  arteries  are  thus  closed  without  the 
operator  having  touched  the  heart.  Prompt  arrest  with  tumultuous  fibrillary 
contractions  follows.  There  seems,  then,  to  be  no  doubt  that  fibrillary  contrac- 
tions can  be  brought  on  bv  sudden  anaemia  of  the  heart  muscle.1 

The  gradual  interruption  of  the  circulation  in  the  coronary  vessels — by 
bleeding  from  the  carotid  artery,  for  example — is  followed  by  feeble  inco- 
ordinated  contractions  not  essentially  different  in  kind  from  those  commonly 
termed  fibrillary  contractions.  The  manner  of  interruption  probably  explains 
the  difference  in  result.  In  the  former  case,  namely,  ligation  or  other  sudden 
closure,  the  supply  of  blood  to  the  heart  muscle  is  suddenly  slopped  while  the 
heart  continues  to  work  against  a  high  peripheral  resistance  ;  in  the  latter,  the 
anaemia  is  gradual  and  the  heart  works  against  little  or  no  peripheral  resistance. 

Recovery  from  Fibrillary  Contractions. — Fibrillary  contract  ions  brought 
on  by  clamping  the  left  coronary  artery  in  the  rabbit's  heart  are  often  gradually 
replaced  by  normal  contractions  when  the  clamp  is  removed.  The  isolated 
cat's  heart  after  showing  marked  fibrillary  contractions  during  forty-five 
minutes  lias  given  strong  regular  beats  for  more  than  an  hour.  McWilliam 
and  others  have  seen  a  number  of  spontaneous  regular  beats  after  the  termi- 
nation of  fibrillary  contraction.  The  dog's  heart  can  be  recovered  by  cool- 
ing the  ventricles  until  all  trace  of  fibrillation  has  disappeared,  and  then 
bringing  the  hearf  back  to  normal  temperature  by  circulating  warmed  defi- 
1  Porter:  Journal  oj   Experimentul  Medicine,  1896,  I.  p.  65. 


184 


AN  AMERICAN    TEXT-BOOK    OE  PHYSIOLOGY. 


brinated  blood  through  the  coronary  vessels.1  Recovery  has  also  been  obtained 
by  passing  immediately  (within  15  seconds)  a  very  rapid  alternating  current 
of  not  too  great  intensity.2 

Closure  of  the  Coronary  Veins. — Closure  of  all  the  coronary  veins  in 
the  rabbit  produced  fibrillary  contractions  alter  from  fifteen  to  twenty  minutes 
had  passed.  Their  closure  in  the  dog  is  said  to  be  without  effect3 — a  negative 
result  perhaps  to  be  explained  by  the  fact  that  a  portion  of  the  coronary  blood 
finds  its  way  to  the  cavities  of  the  heart  through  the  venae  Thebesii. 

Volume  of  Coronary  Circulation. — Bohr  and  Henriques,4  taking  the 
average  of  six  experiments  on  dogs,  found  that  16  cubic  centimeters  of  blood 
passed  through  the  coronary  arteries  per  minute  for  each  100  grams  of  heart 
muscle.  The  quantity  passing  through  both  coronary  arteries  varied  in  dif- 
ferent animals  from  20  to  64  cubic  centimeters  per  minute;  the  quantity 
passing  through   the  left  coronary  artery  varied  from  22.5  to  60  cubic  centi- 


mm 


^^mmmmmm^M-u^ 


U-44-f4WirWW^ 


Fig.  40.— Diminution  of  the  force  of  contraction  of  the  ventricle  of  the  Isolated  cat's  heart  in  con- 
sequence of  diminishing  the  supply  of  blood  to  the  cardiac  muscle  :  A,  blood-pressure  at  the  root  of  the 
aorta,  recorded  bya  mercury  manometer;  B,  intra-ventrieular  pressure-curve,  left  ventricle:  the  indi- 
vidual beats  do  not  appear,  l ause  of  the  slow  >i d  of  the  smoked  surface;  C,  time  in  seconds;  D,  the 

number  of  drops  of  blood  passing  through  the  coronary  arteries,  each  vertical  mark  recording  one  drop. 
As  the  number  of  drops  of  blood  passing  through  the  coronary  arteries  diminishes,  the  contractions  of 
the  hit  ventricle  become  weaker,  but  ret-over  again  when  the  former  volume  of  the  coronary  circula- 
tion Is  restored. 

meters  per  minute.  The  hearts  weighed  from  51  to  350  grams.  The  method 
which  Bohr  and  Henriques  found  it  necessary  to  employ  placed  the  hear! 
under  such  abnormal  conditions  that  their  results  can  be  regarded  as  only 
approximate.  Porter8  supplied  the  left  coronary  artery  of  the  dog  with  blood 
diluted  one-half  with  sodium  chloride  solution  (0.6  per  cent.)  by  means  of  a 
tube  ( lumen  2.75  millimeters  I  inserted  into  the  aortic  opening  of  the  left  coro- 

1  Porter:  American  Journal  of  Physiology,  L898,  i.  p.  71. 

2  Prevost  and  Battelli  :  Journal  de  physiologie  it  de  paihologie  generate,  1900,  p.  440. 
'Michaelis:  Zeitsehrift  fur  klinische  Median,  L894,  xxiv.  |>.  291. 

*  Bohr  and  Henriques:  Skandinavisches  Archivfur  Physiologie,  1895,  v.  p.  232. 
iter:  Journal  of  Experimental  Medicine,  1896,  i.  p.  64. 


CIRCULATION.  185 

nary  artery  and  connected  with  a  reservoir  placed  150  centimeters  above  the 
heart.  In  one  dog,  weighing  11,500  grams,  318  cubic  centimeters  flowed 
through  in  eight  minutes.  In  a  second  dog,  weighing  9500  grams,  114  cubic 
centimeters  passed  through  in  four  minutes.  In  the  isolated  heart  of  the  caf 
strong  and  regular  contractions  are  made  on  a  circulation  of  about  4  cubic 
centimeters  per  minute,  or  even  less,  through  the  coronary  system.  The 
quantity  passing  through  the  veins  of  Thebesius  into  the  left  auricle  and 
ventricle  is  very  slight. 

The  supply  of  blood  to  the  heart-muscle  is  modified  by  ventricular  con- 
traction, not  only  in  that  the  mean  blood-pressure  in  the  aorta  is  a  function 
of  the  force  of  the  heart-beat,  but  directly  by  the  compression  of  the  intra- 
mural vessels  during  systole.  Thus,  when  a  piece  of  the  mammalian  ven- 
tricle is  kept  beating  by  supplying  it  with  defibrinated  blood  through  its 
nutrient  artery  at  a  constant  pressure,  each  beat  can  be  seen  to  force  the  blood 
out  of  the  severed  vessels  in  the  margin  of  the  fragment.  The  effect  of  the 
contractions  on  the  contents  of  the  intramural  vessels  can  also  be  demon- 
strated in  the  living  animal  by  incising  a  vein,  or  a  ligated  artery  on  the 
distal  side  of  the  ligature,  and  slowing  the  heart  by  stimulation  of  the  vagus. 
At  each  systole  of  the  ventricle  blood  is  forced  from  the  vessel.  More- 
over, lessening  the  frequency  of  contraction  diminishes  the  volume  of  the  coro- 
nary circulation — i.  e.,  the  outflow  from  the  coronary  veins,  as  may  be  shown 
in  a  record  similar  to  that  illustrated  by  Fig.  40.  It  is  conceivable  that 
the  emptying  of  the  intramural  vessels  by  the  contraction  of  the  heart  may 
favor  the  flow  of  blood  through  the  heart-walls  in  two  ways:  first,  by  the 
diminished  resistance  which  the  empty  patulous  vessels  should  offer  to  the 
inflow  of  blood  from  the  aorta  when  the  heart  relaxes  ;  and,  secondly,  by 
the  suction  which  might  accompany  the  sudden  expansion  of  the  compressed 
vessels — expanding  either  by  virtue  of  their  intrinsic  elasticity,  or  because 
of  the  pull  of  the  surrounding  tissues  upon  their  walls,  as  the  heart  quickly 
regains  its  diastolic  form.  The  problem  thus  raised  may  be  attacked  by  sud- 
denly connecting  the  distal  portion  of  a  coronary  artery  in  the  strongly  beat- 
ing heart  of  the  living  animal  with  a  small  reservoir  <>f  normally  warm  de- 
fibrinated blood  at  the  atmospheric  pressure.  The  connection  can  be  made 
through  a  cannula  tied  into  the  artery  (ramus  descendens  of  the  dog)  or 
through  a  tube  passed  into  the  left  coronary  artery  by  way  of  the  innominate 
artery  and  aorta.  If  each  compression  of  the  deeper  branches  of  the  artery 
were  followed  by  an  expansion  sufficient  to  cause  a  noteworthy  suction,  the 
blood  in  the  reservoir  should  be  drawn  into  the  artery,  for  this  blood  is  the 
sole  source  of  supply  throughout  the  experiment,  as  the  "  terminal  "  nature 
of  the  coronary  arteries  prevents  any  material  backflo\n  from  the  distal 
branches.  The  results  of  these  experiments  showed  that  no  appreciable  suc- 
tion can  be  demonstrated  in  the  larger  coronary  arteries,  even  when  a  very 
sensitive  minimum  valve  is  interposed  between  the  artery  and  the  reservoir 
in  order  to  prevent  the  possible  masking  of  the  suction  b\  rising  pressure 
accompanying  the  contraction  of  the  ventricle.      It   is,  therefore,  necessary 


186  IV     AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

to  conclude  that  the  emptying  of  the  intramural  vessels  by  the  contraction 

of  the  heart  favors  the  flow  of  blood  through  the  heart-walls  chiefly  by  the 
diminished  resistance  which  the  empty  patulous  vessels  offer  to  the  inflow 
from  the  aorta   when  the  heart  relaxes.1 

The  Vessels  of  Thebesius  and  the  Coronary  Veins. — The  vessels  of 
Thebesius  probably  have  a  part  in  the  nutrition  of  the  heart.  If  a  glass  tube 
two  or  three  inches  long  is  tied  into  the  ventricle  of  the  extirpated  heart  of 
the  cat  and  tilled  with  warm  defibrinated  blood,  the  heart  will  begin  to  beat, 
and,  it'  the  blood  is  oxygenated  from  time  to  time,  may  continue  its  contrac- 
tions tor  many  hours,  although  its  only  supply  is  through  the  vessels  of  The- 
besius. If  a  vein  on  the  surface  of  the  ventricle  is  incised,  the  blood  which 
enters  the  ventricle  arterial  in  color  will  emerge  from  the  cut  vein  a  dark 
venous  hue.  showing  that  it  has  given  up  its  oxygen  and  presumably  other 
nutrient  substances  on  its  way  through  the  heart-wall.  This  experiment  also 
demonstrates  a  connection  between  the  coronary  vessels  and  the  vessels  of 
Thebesius  ;  the  same  may  be  shown  by  corrosion  preparations  of  hearts,  the 
veins  of  which  have  been  injected  with  celloidin. 

The  extirpated  heart  may  be  kept  contracting  a  longer  time,  when  to  the 
supply  received  through  the  vessels  of  Thebesius  is  added  that  which  may 
reach  the  heart  from  the  auricle  by  baekffow  through  the  coronary  veins,  the 
valves  of  which  are  incompetent. 

It  is  evident  that  these  accessory  channels  of  nutrition  must  be  of  impor- 
tance when  the  main  supply  through  the  arteries  is  diminished,  as  in  arterio- 
sclerosis.2 

Blood-supply  and  Heart-beat. — The  relation  between  the  volume  of 
blood  passing  through  the  coronary  arteries  and  the  rate  and  force  of  the 
ventricular  contraction  has  been  studied  by  Magrath  and  Kennedy.3  Varia- 
tions in  the  volume  of  the  coronary  circulation  in  the  isolated  heart  of  the 
cat,  unless  very  considerable,  are  not  accompanied  by  changes  in  the  rate 
of  beat.  The  force  of  contraction,  on  the  contrary,  appears  to  be  closely 
dependent  on  the  volume  of  the  coronary  circulation  (Fig.  40). 

Distention  of  the  ventricle  diminishes  the  volume  of  blood  flowing 
through  the  coronary  vessels,  except  when  this  effect  is  compensated  by  the 
distention  stimulating  the  ventricle  to  contract  more  forcibly,  and  thus  to 
pump  more  blood  through  its  walls  by  alternate  compression  and  expansion 
of  the  intramural  vessels.4 

Lymphatics  of  the  Heart. — A  rich  plexus  of  lymphatic  vessels  has  been 
demonstrated  in  the  heart.8  Valuable  information  concerning  the  nutrition  of 
the  hearl  could  probably  be  gained  by  the  systematic  study  of  these  vessels. 

1  Porter:   American  Journal  "/  Physiology,  1S9S,  i.  p.  145;    consult  also  von  Vintschgau : 
Archiv  jiir  die  gesammte  I'hysiolor/ie,  1890,  lxiv.  p.  79. 
-  Pratt:   Tbid.,  p.  86. 
:;  Magrath  and  Kennedy:  Journal  of  Experimental  Medicine,  1897,  ii.  p.  13. 

4  I.  II.  Hyde:    American  Journal  of  Physiology,  1898,  i.  p.  215. 

5  Nystroin  :   Archiv  fur  Physiologie,  1897,  p.  361. 


CIBCULA  TION. 


187 


0.  Solutions  which  Maintain  the  Beat  of  the  Heart. 

The  beat  of  the  heart  is  maintained  during  life  by  a  constant  supply  of 
oxygenated  blood.  The  blood,  however,  is  a  very  complex  fluid,  and  it  can 
hardly  be  supposed  that  all  of  its  constituents  are  of  equal  value  to  the  heart. 
The  systematic  search  for  those  constituents  of  the  blood  which  are  of  import- 
ance to  the  nutrition  of  the  heart  was  begun  in  Lud  wig's  laboratory  iu  1875 
by  Merunowicz.  The  first  step  toward  the  method  used  by  Merunowicz  and 
his  successors  was  taken  by  ('yon.  Cyon  tied  cannulas  in  the  vena  cava 
inferior  and  in  one  of  the  aortse  of  the  extirpated  heart  of  the  frog,  and 
joined  them  by  a  bowed  tube  filled  with  serum.  The  ventricle  pumped 
the  serum  through  the  aortic  cannula  and  the  bowed  tube  into  the  vena 
cava,  whence  it  reached  the  ventricle  again.  The  force  of  the  contraction 
was  measured  by  a  mercury  manometer  which  was  joined  by  a  side  branch 
to  one  limb  of  the  bowed  tube. 

The  frog  heart  manometer  method  thus  introduced  by  Ludwig  and  (yon 
has  undergone  various  modifications  at  the  hands  of  Blasius  and  Fick,  Bow- 
ditch,  Luciani,  Kronecker,  and  others.  Blasius  and  Fick  were  the  firs!  to 
register  changes  in  the  volume  of  the  heart  by  the  plethysmography  method, 
the  organ  being  enclosed  in  a  vessel  filled  with  normal  saline  solution  and 
connected  with  a  manometer.  This  idea  reappears  in  the  Strassburg  apparatus 
described  below. 

A  valuable  improvement  was  made  by  Kronecker,  who  invented  a  double 
cannula,  through  one  side  of  which  the  "  nutrient "  fluid  enters  the  ventricle 
while  it  passes  out  through  the  other  (Fig.  4 1 ). 
The  contents  of  the  ventricle  are  thus  contin- 
ually renewed.  In  1878,  Hoy  constructed  the 
instrument  shown  in  Figure  42,  by  means  of 
which  the  changes  in  the  volume  of  the  heart  at 
each  contraction  are  recorded  on  a  moving  cylin- 
der. A  great  advance  was  made  by  Williams, 
in  the  invention  known  as  "  Williams's  valve," 
which  is  the  essential  feature  of  the  apparatus 
devised  by  this  investigator  and  others  in 
Schmiedeberg's  laboratory  at  Strassburg.  The 
present  form  of  this  apparatus  is  illustrated  in 
Figure  43.  A  perfusion  cannula  is  introduced 
into  the  ventricle  through  the  aorta.  Through 
one  tube  of  the  cannula  the  heart  is  fed  from  a 
reservoir  placed  above  it.  Through  the  other 
the  heart  pumps  its  contents  into  a  higher  reser- 
voir or  into  the  same  reservoir.  Thus  the  heart  is  "  Loaded  "  with  a  column 
of  liquid  of  known  height  and  pumps  againsl  ;i  measurable  resistance.  A 
Williams  valve  in  the  inflow  lube  prevents  any  flow  except  in  the  direction 
of  the  heart.     A  similar  valve  reversed  in  the  outflow  tube  prevents  any  How 


Fig.  41.— The  perfusion  cannula 
of  Kronecker.  The  ventricle  is  tied 
..n  the  cannula  at  d,  a  ring  heing 
placed  here  to  prevent  the  ligature 
from  slipping.  The  double  tube, 
shown  in  cross  section  at  ■ ,  'li\  Idea 
into  the  large   brani  b  a  and   the 

small  branch  6,  The  nutrient  BOlU- 
tinn  enters  tic  bearl  through  '-  and 
escapee  through  <<.  The  Bilver  wire 
e  can  ho  connected  \\  Itb  one  pole  of 
11  battery,  the  cannt  ae  one 

electrode, and  the  fluid  Burrounding 
the  bearl  as  i be  other. 


188 


AN    AMERICAN    TEXT-HOOK    OF    PHYSIOLOGY 


except  away  from  the  heart.  The  ventricle  is  rilled  and  emptied  alternately  as 
is  the  normal  heart,  the  artificial  valves  replacing  the  heart-valves,  which  are 
often  necessarily  rendered  useless  by  the  introduction  of  the  cannula  and  are  at 
best  less  certain  in  their  action  than  the  artificial  valve.  The  changes  in  the 
volume  of  the  heart  are  shown  by  the  movements  of  a  liquid  column  in  a 


Fig.  42— Roy's  apparatus:  the  heart  is  tied  on  a 
perfusion  cannula  and  enclosed  in  a  bell  glass  rest- 
in-  ..ii  a  brass  plate,?*, the  centre  of  which  presents 
an  opening  covered  by  a  rubber  membrane.  Vari- 
ations in  the  volume  of  the  heart  cause  the  mem- 
brane to  rise  and  fall.  The  movements  of  the 
membrane  are  recorded  by  a  lever. 


Fig.  43.— Williams's  apparatus:  H,  frog's  heart; 
V,V,  Williams's  valves  ;  MS,  millimeter  scale.  The 
apparatus  is  arranged  to  feed  the  heart  from  the 
reservoir  into  which  the  heart  is  pumping. 


horizontal  tube  which  communicates  with  the  bottle  filled  with  "nutrient" 
fluid  in  which  the  heart  is  enclosed. 

In  the  original  method  of  Cyon  the  ventricle  is  left  in  connection  with  the 
auricle,  the  ganglion-cells  of  the  ventricle  and  the  neighboring  portions  of  the 
auricle  being  kept  intact.  This  "whole  heart"  preparation  is  to  be  distin- 
guished from  the  "apex"  preparation  of  Bowditch,  which  has  also  been  used 
in  studies  of  the  effects  of  nutrient  solutions  on  the  heart.  In  Bowditeh's 
"apex"  preparation,  the  ventricle  is  bound  to  the  cannula  by  a  thread  tied  at 
the  junction  of  the  upper  and  middle  thirds  of  the  ventricle.  By  this  means 
the  lower  two-thirds  of  the  ventricle,  which  contains  no  ganglion-cells,  is  cut 
off  from  any  physiological  connection  with  the  base  of  the  ventricle  and  a 
"  ganglion-free  apex  "  secured.  The  isolated  "  apex "  at  first  stands  still,  but 
after  from  ten  to  sixty  minutes  commences  to  beat  again  and  can  then  be  kept 
beating  for  several  hours. 

In  the  use  of  these  various  methods  certain  general  precautions  should  be 
kept  in  mind.  Special  attention  should  be  directed  to  the  difficulty  of  remov- 
ing the  blood  from  the  capillary  fissures  in  the  wall  of  the  frog's  heart.  A 
small  amount  of  blood  remaining  in  these  passages  is  frequently  a  source  of 
error.  It  should  be  remembered  that,  as  Cyon  pointed  out,  a  change  in  the 
nutrient  solution  is  of  itself  a  stimulus  to  the  heart,  increasing  or  diminishing 
the  frequency  of  contraction  and  obliging  the  investigator  to  wait  until  the  heart 


CIRCULATION.  189 

has  become  accustomed  to  the  new  solution  before  making  an  observation.  The 
heart  should,  as  a  rule,  be  constantly  supplied  with  fresh  fluid,  as  in  the  natural 
state.  The  resistance  against  which  the  heart  works  is  also  a  factor  of  import- 
ance. The  water  with  which  the  solutions  are  made  should  be  distilled  in  glass, 
as  the  minutest  trace  of  the  compounds  of  heavy  metals  in  non-colloidal  solu- 
tions affects  the  heart.1 

Nutrient  Solutions. — Cyon  found  that  the  beat  of  the  extirpated  frog's 
heart  is  very  dependent  on  the  nature  of  the  solution  with  which  the  heart  is 
fed.  Hearts  supplied  with  normal  saline  solution  (NaCl,  0.6  per  cent.)  ceased 
to  beat  much  sooner  than  those  left  empty.  The  serum  of  dog's  blood  seemed 
almost  poisonous.  Rabbit's  serum,  on  the  contrary,  postponed  the  exhaustion 
of  the  heart  for  many  hours,  provided  the  limited  quantity  contained  in  the 
apparatus  was  renewed  from  time  to  time.  Serum  used  over  and  over  again 
caused  the  beats  to  lose  force  after  an  hour  or  two.  The  renewal  of  the  serum 
seemed  a  stimulus  to  the  heart,  causing  it  to  contract  very  strongly  during  a 
half  minute  or  more,  after  which  the  contractions  became  less  energetic. 

Cyon's  immediate  successors,  Bowditch,  Luciani,  and  Rossbach,  confirmed 
his  observations.  None  of  these  investigators,  however,  was  concerned  pri- 
marily with  the  nutrition  of  the  heart.  The  first  systematic  work  on  this  sub- 
ject was  done,  as  has  been  said,  by  Meruuowicz,  who  attempted  to  maintain 
the  beat  of  the  heart  with  normal  saline  solution  containing  various  quantities 
of  blood,  with  normal  saline  alone,  with  a  watery  solution  of  the  ash  of  an 
alcholic  extract  of  serum,  and  with  a  normal  saline  solution  containing  a 
minute  amount  of  sodium  carbonate.  The  direction  taken  by  him  has  been 
pursued  to  the  present  day,  the  chief  objects  of  study  being  the  importance  to 
the  heart  of  sodium  carbonate  or  other  alkali,  sodium  and  potassium  chloride, 
the  salts  of  calcium,  oxygen,  proteids  and  some  other  organic  bodies  such  as 
dextrose,  and,  finally,  of  fluids  possessing  the  physical  characteristics  of  the 
blood.     The  outcome  of  this  work   we  must  now  consider. 

The  value  of  an  alkaline  reaction  has  been  generally  recognized.  Sodium 
carbonate  is  the  alkali  commouly  preferred.  The  favorable  influence  of  this 
salt  probably  does  not  depend  on  any  specific  action,  but  simply  upon  its 
alkalinity.  The  alkali  promotes  the  beat  of  the  heart  by  neutralizing  the 
carbon  dioxide  and  other  acids  formed  in  the  metabolism  of  the  contracting 
muscle;  this,  however,   may  not  be  its  only  use. 

Certain  of  the  salts  normally  present  in  the  blood  are  necessary  i"  main- 
tain the  beat  of  the  heart.  Sodium  chloride  is  one  of  these.  The  solution 
employed  should  contain  a  "  physiological  quantity."  Such  a  solution  is  said 
to  be  "  isotonic."  The  amount  required  t<»  make  a  sodium  chloride  solution 
"normal"  or  "  isotonic"  for  the  frog  is  <).(>  per  cent.,  for  the  mammal  Dearly 
1  per  cent.  Enough  of  a  calcium  salt  to  prevent  the  washing  ouf  of  lime 
from  the  tissues  is  also  essential  for  prolonged  maintenance  of  the  contractions. 
A  heart  fed  with  normal  saline  solution  is  before  long  brought  t<>  a  stand  ;  the 
addition  of  a  calcium  salt  to  the  solution  postpones  the  arrest.  The  character 
'Locke:  Journal  of  Physiology,  lK'.t.">,  xviii.  p,  331. 


190  AN   AMERICA*    TEXT-BOOK    OF   PHYSIOLOGY. 

of  the  contraction,  however,  is  altered  by  the  calcium,  the  relaxation  of  the 
ventricle  being  sometimes  so  much  delayed  that  the  next  contraction  takes 
place  before  the  relaxation  from  the  previous  contraction  has  commenced,  the 
ventricle  falling-  thereby  into  a  state  of  persistent  or  "  tonic"  contraction.  The 
additiou  of  a  potassium  sail  restores  the  normal  character  of  the  contraction, 
calcium  and  potassium  having  an  antagonistic  action  on  the  heart.1  The 
importance  of  calcium  to  the  heart  is  said  to  be  demonstrated  by  the  disap- 
pearance of  the  spontaneous  contractions  of  the  heart  which  follows  the  pre- 
cipitation of  the  calcium  in  the  circulating  fluid  by  the  addition  to  it  of  an 
equivalent  quantity  of  a  soluble  oxalate,  and  by  the  return  of  spontaneous 
contractions  which  is  seen   when  the  calcium   is  restored  to  the  solution. 

The  antagonistic  action  of  calcium  and  the  oxalates  was  first  pointed  out 
by  (yon. 

According;  to  Ringer,  the  substances  thus  far  mentioned  are  effective  in  the 
following  order :  normal  saline  is  the  least  effective;  next  is  saline  containing 
sodium  bicarbonate;  then  saline  containing  tricalcium  phosphate;  and  best  of 
all,  saline  containing  tricalcium  phosphate  together  with  potassium  chloride. 
He  recommends  the  following  mixture:  Sodium  chloride  solution  ().(>  per 
cent.,  saturated  with  tribasic  calcium  phosphate,  100  cubic  centimeters;  solu- 
tion potassium  chloride  1  per  cent.,  or  acid  potassium  phosphate  (HK2POJ 
1  per  cent.,  2  cubic  centimeters.2 

There  has  been  considerable  dispute  over  the  part  played  by  oxygen  in 
the  beat  of  the  frog's  heart.  McGuire  and  Klug  were  of  opinion  that 
the  beat  is  largely  independent  of  the  amount  of  oxygen  in  the  circulating 
fluid.  Yeo  concluded  that  the  contracting  heart  uses  more  oxygen  than 
the  resting  heart,  and  that  the  consumption  of  oxygen  increases  with  the  work 
done.  Kronecker  and  Handler,  on  the  contrary,  believe  that  the  oxygen  con- 
sumption is  increased  by  an  increase  in  the  rate  of  beat,  but  is  independent  of 
the  work  done.  More  recent  observers  are  united  on  the  necessity  of  oxygen 
to  the  working  heart.  Oehrwall's  studies  in  this  field  are  especially  interesting. 
He  finds  that  a  volume  of  blood  sufficient  to  fill  the  frog's  ventricle  will  main- 
tain contractions  for  hours  provided  the  heart  is  surrounded  by  an  atmosphere  of 
oxygen.  The  heart  is  brought  to  a  stand  by  lack  of  oxygen  and  may  be  made 
to  beat  again,  even  after  an  arrest  of  twenty  minutes,  by  giving  it  a  fresh  sup- 
ply. The  heart  fails  in  oxygen-hunger  probably  because  the  chemical  process 
by  which  the  stimulus  to  contraction  is  called  forth  no  longer  takes  place,  and 
not  because  of  a  failure  in  contractility,  for  even  after  long  inaction  a  gentle 
touch  on  the  pericardium  will  cause  a  vigorous  contraction.'5 

Haldane4  discovered  that  the  corpuscles  of  the  blood  are  not  essential  to 
the  contractions  of  the  warm-blooded  heart,  provided  the  oxygen  which  the 

'Bottazzi:  Archives  de  Physiologic,  L896,  xxviii.  p.  882. 
Ringer  :  Journal  of  Phusiolixjij,  1893,  xiv.  p.  128.     The  bibliography  has  recently  been  given 
by  Unwell:    American  Journal  of  Physiology,  1898,  ii.  p.  47  ;  and  Greene  :  Ibid.,  p.82;  consult 
also  White  :  Journal  of  Physiology,  1896,  xix.  p.  344. 

Oehrwall:  Skandinavisches  Archivfur  Physiologic,  1898,  viii.  p.  1. 
*  Haldane:  Journal  of  Physiology,  1895,  xviii.  p.  211. 


CIRCULATION.  191 

heart  needs  is  supplied  by  increasing  the  tension  of  the  gas  in  the  plasma. 
Haldane  kept  his  animals  alive  in  oxygen  at  a  pressure  of  two  atmospheres 
after  the  oxygen-carrying  function  of  the  red  corpuscles  had  been  destroyed 
with  carbon  monoxide.  The  experiment  has  been  repeated  with  the  extir- 
pated mammalian  heart  by  Porter,1  Locke,2  and  Rusch.3  Serum  and  even 
saline  solutions  will  serve,  if  the  oxygen  tension  is  high  or  if  the  volume  of 
oxygen  reaching  the  tissues  is  increased  simply  by  causing  the  nutrient  liquid 
to  circulate  more  rapidly. 

Carbon  dioxide4  is  injurious  to  the  heart  when  present  in  the  circulating 
fluid  in  considerable  quantities.  The  force  of  the  contraction  is  reduced  before 
the  rate  of  beat.  The  heart  poisoned  with  carbon  dioxide  often  falls  into 
irregular  contractions,  exhibiting  at  times  "grouping"  and  the  "staircase" 
phenomenon,  a  series  of  beats  regularly  increasing  in  strength. 

Organic  Substances. — An  unsuccessful  effort  has  been  made  to  prove  that 
only  solutions  containing  proteids,  for  example  blood-serum,  chyle,  and  milk, 
can  keep  the  heart  active.  Recent  observers  have  shown  the  incorrectness  of 
this  claim.  A  mixture  of  the  inorganic  salts,  sodium  chloride,  potassium 
chloride,  and  calcium  chloride,  alone  suffices.  Locke5  found  that  tin-  addi- 
tion of  0.1  per  cent,  of  dextrose  to  a  suitable  inorganic  solution  kept  a  frog's 
heart  working  under  a  load  of  3.5  centigrams,  and  under  an  "  after-load  "  of  3 
centigrams  in  spontaneous  activity  for  more  than  twenty-four  hours.  The 
sustaining  action  which  dextrose  appears  to  exercise  is  shared,  according  to  him, 
by  various  other  organic  substances. 

Physical  Characteristics. — Heffter  and  Albanese,6  having  observed  that 
the  addition  of  gum-arabic  to  the  circulating  fluid  was  of  advantage,  declared 
that  the  nutrient  solutions  should  possess  the  viscosity  of  the  blood.  The 
favorable  action  of  gum-arabic  may,  however,  more  probably  be  ascribed  to  the 
compounds  which  it  contains  rather  than  to  its  physical  properties.7 

Mammalian  Heart. — The  success  attained  within  the  past  two  years  in  the 
isolation  of  the  mammalian  heart  opens  up  an  hitherto  unexplored  region  in 
which  systematic  investigation  will  surely  bring  to  light  facts  of  wide  interest 
anil  value.  At  present,  however,  little  is  known  as  to  the  constituents  of  the 
blood  which  are  essential  to  the  life  of  the  mammalian  heart.  An  abundant 
supply  of  oxygen  is  certainly  highly  important.8 

1  Porter:  American  Journal  of  Physiology,  1K9S,  i.  p.  511. 

2  Locke:  Centralblatt fur  Physiologic  1808,  xii.  p.  5(58. 

5  Rusch  :   Archil'  filr  di<>  gesammte  Physiologie,  189S,  lxxiii.  p.  535. 

*Langendorff:  Archivfur  Physiologie,  1893,  p. 417 j  [de:  Ibid.,  p.  492;  Oehrwall:  Skcmdin- 
avisches  Archivfur  Physiologie,  1897,  vii.  p.  222. 

5  Locke:  Journal  of  Physiology,  1895,  xviii.  p.  332. 

6  Albanese:  Archivfur  experimenteUe  Pathologie  unci  Pharmakologie,  1893,  \\\ii.  p.  311; 
Archives  ilaliennes  de  Biologic,  1896,  xxv.  p.  308. 

7  Howell  and  Cooke:  Journal  of  Physiology,  1893,  xiv.  p.  216. 

8  Literature  is  given  by  Magrath  and  Kennedy  :  Journal  of  Experimental  Medicine,  1897,  ii. 
p.  13;  and  I  led  bom  :  Skandinavisches  Archivfur  Physiologie,  1898,  viii.  p.  H7.  See  also  tiering: 
Archivfur  die  gesammte  Physiologie,  1  s'.,s,  lxxii.  p.  163 ;  Bock:  Archiv  fur  experimenteUe  Path- 
ologie und  Pharmakologie,  1898,  xli.  p.  158  ;  and  Cleghorn  :  American  Journal  of  Physiology,  1899, 
ii.  p.  273. 


192  AN    AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

Blood  of  Various  Animals. — Roy  gives  some  data  as  to  the  effect  on  the 
froe's  ventricle  of  the  blood  of  various  animals.  The  blood  of  the  various  her- 
bivora  (rabbit,  guinea-pig,  horse,  cow,  calf,  sheep),  as  well  as  that  of  the  pigeon, 
were  found  to  have  nearly  the  same  nutritive  value  in  each  case.  That  of  the 
dog,  of  the  cat,  and  more  especially  of  the  pig,  while  in  some  instances  equal  in 
effect  to  that  from  the  horse  or  rabbit,  were  in  other  examples  (from  the  newly 
killed  animals)  apparently  almost  poisonous.  Cyon's  early  observation  of  the  in- 
jurious action  of  dog's  blood  on  the  frog's  ventricle  has  already  been  mentioned.1 

Regarding  the  mammalian  heart,  experience  has  shown  that  it  is  best  to 
supply  the  heart  with  blood  from  the  same  species  of  animal.  The  difficulties 
attending  the  use  of  blood  from  a  different  species  are  seen  in  the  case  of  the 
dog's  heart  supplied  with  calf's  blood.  The  heart  dies  sooner;  cedema  of  the 
lungs  takes  place,  impeding  the  pulmonary  circulation  and  leading  to  engorge- 
ment of  the  right  heart  and  paralysis  of  the  right  auricle  ;  exudation  into  the 
pericardium  often  seriously  interferes  with  the  beat  of  the  heart;  and,  finally, 
the  elastic  modulus  of  the  cardiac  muscle  is  apparently  altered,  permitting  the 
heart  to  swell  until  it  tightly  fills  the  pericardium,  when  the  proper  filling  of 
the  heart  is  no  longer  possible  through  lack  of  room  for  diastolic  expansion. 


PART   IV.— THE   INNERVATION   OF   THE   BLOOD- VESSELS.2 

About  the  middle  of  the  eighteenth  century  more  or  less  sagacious  hypotheses 
concerning  the  contractility  of  the  blood-vessels  began  to  appear  in  medical 
literature,  but  it  was  not  until  Ifenle  demonstrated  the  existence  of  muscular 
elements  in  the  middle  coats  of  the  arteries  in  1840  that  a  secure  foundation 
was  laid  for  the  present  knowledge  of  the  mechanism  by  which  that  contractility 
is  made  to  control  the  distribution  of  the  blood.  More  than  a  hundred  years 
before,  indeed,  Pourfour  du  Petit  had  shown  that  redness  of  the  conjunctiva 
was  one  of  the  consequences  of  the  section  of  the  cervical  sympathetic,  but  had 
called  the  process  an  inflammation,  in  which  false  idea  he  was  supported  by 
Cruikshank  and  others;  and  Dupuy  of  Alfort  had  noted  redness  of  the  con- 
junctiva, increased  warmth  of  the  forehead,  and  sweat-drops  on  ears,  forehead, 
and  neck  following  his  extirpation  of  the  superior  cervical  ganglia  in  the 
horse;  Brachet,  also,  cutting  the  cervical  sympathetic  in  the  dog,  had  gone  so 
far  as  to  attribute  the  resulting  congestion  to  a  paralysis  of  the  blood-vessels. 
Hut  the-e  were  merely  clever  -peculations,  for  the  anatomical  basis  necessary 
for  a  real  knowledge  of  this  subject  was  wanting  as  yet.  Henlc  furnished  this 
basis, and  at  the  same  time  reached  the  modern  point  of  view.  ''The  part 
taken  by  the  contractility  of  the  heart  and  the  blood-vessels  in  the  circulation," 
-aid  Henle,  "can  be  expressed  in  two  words:  the  movement  of  the  blood  depends 
on  the  heart,  but  its  distribution  depends  on  the  vessels."  Nor  did  Henlc;  stop 
here.      It  was  now   known  that  the  vessels  possessed  contractile  walls ;  it  was 

1  See  also  Bardier:  Comptes  rend/us  Societi  de  Biologic,  1898,  p.  548. 
'See  footnote  t<>  Part  II.,  p.  lis. 


CIRCULATION.  193 

known  further  that  these  walls  contracted  when  mechanically  stimulated;  for 
example,  by  scraping  them  with  the  point  of  a  scalpel  ;  and  various  observers 
had  traced  sympathetic  nerves  from  the  greater  vessels  to  the  lesser  until  lost  in 
their  finest  ramifications.  It  was  therefore  easy  to  construct  a  reasonable 
hypothesis  of  the  control  of  the  blood-vessels  by  the  nerves.  Henle  declared 
that  the  vessels  contract  because  their  nerves  are  stimulated,  either  directly, 
or  reflexly  through  the  agency  of  a  sensory  apparatus.  The  ground  was 
thus  prepared  for  the  physiological  demonstration  of  the  existence  of  "  vaso- 
motor" nerves,  as  Stilling  began  to  call  them.  Four  names  are  associated 
with  this  great  achievement — Schiff,  Bernard,  Brown-Sequard,  and  Waller, 
each  of  whom  worked  independently  of  the  others.  Foremost  among  them 
is  Claude  Bernard,  though  not  the  first  in  point  of  time,  for  it  was  he  who 
put  the  new  doctrine  on  a  firm  basis.  In  his  first  publication  Bernard  stated 
that  section  of  the  cervical  sympathetic,  or  removal  of  the  superior  cervical 
ganglion,  in  the  rabbit,  causes  a  more  active  circulation  on  the  correspond- 
ing side  of  the  face  together  with  an  increase  in  its  temperature.  The  greater 
blood-supply  manifests  itself  in  the  increased  redness  of  the  skin,  particularly 
noticeable  in  the  skin  of  the  ear.  The  elevation  of  temperature  may  be  easily 
felt  by  the  hand.  A  thermometer  placed  in  the  nostril  or  in  the  ear  of  the 
operated  side  shows  a  rise  of  from  4°  to  6°  C  The  elevation  of  temperature 
may  persist  for  several  months.  Similar  results  are  obtained  in  the  horse  and 
the  dog. 

The  following  year  Brown-Sequard  announced  that "  if  galvanism  is  applied 
to  the  superior  portion  of  the  sympathetic  after  it  has  been  cut  in  the  neck,  the 
dilated  vessels  of  the  face  and  of  the  ear  after  a  certain  time  begin  to  contract ; 
their  contraction  increases  slowly,  but  at  last  it  is  evident  that  they  resume 
their  normal  condition,  if  they  are  not  even  smaller.  Then  the  temperature 
diminishes  in  the  face  and  the  ear,  and  becomes  in  the  palsied  side  the  same  as 
in  the  sound  side.  When  the  galvanic  current  ceases  to  act,  the  vessels  begin 
to  dilate  again,  and  all  the  phenomena  discovered  by  Dr.  Bernard  reappear." 
Brown-Sequard  concludes  that  "the  only  direct  effect  of  the  section  of  the 
cervical  part  of  the  sympathetic  is  the  paralysis,  and  consequently  the  dilata- 
tion, of  the  blood-vessels.  Another  evident  conclusion  is  that  the  cervical 
sympathetic  sends  motor  fibres  to  many  of  the  blood-vessels  of  the  head." 

While  Brown-Sequard  was  making  these  important  investigations  in 
America,  Bernard,  in  Paris,  quite  unaware  of  Brown-Kequard's  labors,  was 
reaching  the  same  result.  The  existence  of  nerve-fibres  the  stimulation  of 
which  causes  constriction  of  the  blood-vessels  to  which  they  are  distributed  was 
thus  established. 

A  considerable  addition  to  this  knowledge  was  presently  made  by  Schiff, 
who  pointed  out  in  185b'  that  certain  vaso-motor  nerves  take  origin  from  the 
spinal  cord.  The  destruction  of  certain  parts  of  the  spinal  cord  causes  the 
same  vascular  dilatation  and  rise  of  temperature  that  follows  the  section  of  the 
vaso-motor  nerves  outside  the  spinal  cord. 

At  this  time  Schiff  also  offered  evidence  of  vaso-dilator  nerves.  When 
Vol.  I.— 13 


194  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

the  left  cervical  sympathetic  is  cut  in  a  dog,  and  the  animal  is  kept  in  his 
kennel,  (he  left  ear  will  always  be  found  to  be  5°  to  9°  warmer  than  the 
right,  [f  the  dog  is  now  taken  out  for  a  run  in  the  warm  sunshine,  and 
allowed  to  heat  himself  until  he  begins  to  pant  witli  outstretched  tongue,  the 
temperature  of  both  ears  will  lie  found  to  have  increased.  The  right  ear  is 
now,  however,  the  warmer  of  the  two,  being  from  1°  to  5°  warmer  than  the 
left.  The  blood-vessels  of  the  right  ear  are,  moreover,  now  fuller  than  those 
of  the  left.  When  the  animal  is  quiet  again  the  former  condition  returns,  the 
redness  and  warmth  in  the  right  becoming  again  less  than  in  the  left  ear.  The 
increase  of  the  redness  and  warmth  of  the  right  ear  over  the  left,  in  which  the 
vaso-constrictor  nerves  were  paralyzed,  must  be  the  result  of  a  dilatation  of 
the  vessels  of  the  right  ear  by  some  nervous  mechanism.  For  if  the  dilatation 
of  the  vessels  was  merely  passive,  the  vessels  in  the  right  ear  cotdd  not  dilate  to 
a  greater  degree  than  those  in  the  left  ear  which  had  been  left  in  a  passive  state 
by  the  section  of  their  nerves.  This  experiment,  however,  is  by  no  means  con- 
el  nsive. 

The  existence  of  vaso-dilator  fibres  was  placed  beyond  doubt  by  the  follow- 
ing experiment  of  Bernard  on  the  chorda  tympani  nerve,  new  facts  regarding 
the  vaso-constrietor  nerves  being  also  secured.  Bernard  exposed  the  submax- 
illary gland  of  a  digesting  dog,  removed  the  digastric  muscle,  isolated  the 
nerves  going  to  the  gland,  introduced  a  tube  into  the  duct,  and,  finally,  sought 
out  aud  opened  the  submaxillary  vein.  The  blood  contained  in  the  vein  was 
dark.  The  nerve-branch  coming  to  the  gland  from  the  sympathetic  wTas  now 
ligated,  whereupon  the  venous  blood  from  the  gland  grew  red  and  flowed  more 
abundantly;  no  saliva  was  excreted.  The  sympathetic  nerve  was  now  stimu- 
lated between  the  ligature  and  the  gland.  At  this  the  blood  in  the  vein  became 
dark  again,  flowed  in  less  abundance  and  finally  stopped  entirely.  On  allow- 
ing the  animal  to  rest  the  venous  blood  grew  red  once  more.  The  chorda 
tympani  nerve,  coming  from  the  lingual  nerve,  was  now  ligated,  and  the  end 
in  connection  with  the  gland  stimulated.  Then  almost  at  once  saliva  streamed 
into  tiie  duct,  and  large  quantities  of  bright  scarlet  blood  flowed  from  the  vein 
in  jets,  synchronous  with  the  pulse. 

This  experiment  may  be  .-aid  to  close  the  earlier  history  of  the  vaso-motor 
oerves.  It  was  now  established  beyond  question  that  the  size  of  the  blood- 
vessels, and  thus  the  quantity  of  blood  carried  by  them  to  different  parts  of  the 
body,  is  controlled  by  nerves  which  when  stimulated  either  narrow  the  blood 
vessels  (vaso-constrictor  aerves)  and  thus  diminish  the  quantity  of  blood  that 
(lows  through  them,  or  dilate  the  vessels  (vaso-dilator  nerves)  and  increase  the 
flow.  The  section  of  vaso-constrictor  nerves,  for  example  those  found  in  the 
cervical  sympathetic,  causes  the  vessels  previously  constricted  by  them  to  dilate. 
The  section  of  a  vaso-dilator  nerve,  for  example  the  chorda  tympani,  running 
from  the  lingual  nerve  to  the  submaxillary  gland,  does  not.  however,  cause  the 
constriction  of  the  vessels  to  which  it  is  distributed.  And  finally,  it  was  now 
determined  that  vaso-motor  fibres  are  found  in  the  sympathetic  system  as 
well  as  in  the  spinal  cord  and  the  cerebro-spinal  nerves. 


CIRCULATION.  195 

It  remained  for  a  later  day  to  show  that  vasomotor  nerves  arc  present  in 
the  veins  as  well  as  in  the  arteries.  Mall  has  found  that  when  the  aorta  is 
compressed  below  the  left  subclavian  artery,  the  portal  vein  receives  no  more 
blood  from  the  arteries  of  the  intestine,  yet  remains  for  a  time  moderately  full, 
because  it  cannot  immediately  empty  its  contents  through  the  portal  capil- 
laries of  the  liver  against  the  resistance  which  they  offer.  If  the  peripheral 
end  of  the  cut  splanchnic  nerve  is  now  stimulated,  the  portal  vein  contracts 
visibly  and  may  be  almost  wholly  emptied.  Thompson  '  has  extended  the 
discovery  of  Mall  to  the  superficial  veins  of  the  extremities.  He  finds  that 
the  stimulation  of  the  peripheral  end  of  the  cut  sciatic  nerve,  the  crural  arterv 
being  tied,  causes  the  constriction  of  the  superficial  veins  of  the  hind  limb. 
The  contraction  begins  soon  after  the  commencement  of  the  stimulation,  and 
usually  goes  so  far  as  to  obliterate  the  lumen  of  the  vein.  Often  the  contrac- 
tion begins  nearer  the  proximal  portion  of  the  vein  and  advances  toward  the 
periphery.  More  commonly,  however,  it  is  limited  to  band-like  constrictions 
between  which  the  vein  is  filled  with  blood.  After  stimulation  ceases  the 
constrictions  gradually  disappear.  A  second  and  third  stimulation  produce 
much  less  constriction.  The  superficial  veins  of  the  rabbit's  abdomen  are 
constricted  by  the  stimulation  of  the  cervical  spinal  cord  at  the  second  ver- 
tebra. 

The  observations  of  Bernard  and  his  contemporaries  led  to  a  very  great 
number  of  researches  on  the  general  properties  and  the  distribution  of  the 
vaso-motor  nerves,  in  the  course  of  which  a  variety  of  ingenious  methods  of 
observation  have  been  devised. 

Methods  of  Observation. — One  fruitful  method  of  research  has  been 
already  incidentally  mentioned,  namely,  the  direct  inspection  of  the  vessel,  or 
region,  the  vaso-motor  nerves  of  which  are  being  studied. 

A  second  method  consists  in  accurately  measuring  the  outflow  from  the 
vein.  If  the  blood-vessels  of  the  area  drained  by  the  vein  are  constricted  by 
the  stimulation  of  a  vaso-motor  nerve,  the  quantity  escaping  from  the  vein  in 
a  given  period  previous  to  constriction  will  be  greater  than  that  escaping  in  an 
equal  period  during  constriction.  This  well-known  method  is  especially  avail- 
able where  an  artificial  circulation  is  kept  up  through  the  organ  studied,  as 
the  blood  drained  from  the  vein  does  not  then  weaken  the  animal  and  thus 
disturb  the  accuracy  of  the  observations.2 

A  third  method  is  founded  on  the  principle  in  hydraulics  that  the  lateral 
pressure  at  any  point  in  a  tube  through  which  a  liquid  How-  depends,  othei 
things  being  equal,  on  the  resistance  to  be  overcome  below  the  poinl  at  which 
the  pressure  is  measured.  In  the  animal  body  the  resistance  to  be  overcome 
by  the  blood-stream  varies  with  the  state  of  contraction  of  the  smaller  vessels, 
and  thus  the  variations  in  the  lateral  pressure  of  a  given  artery  may.  under 
certain  restrictions,  be  used  to  determine  variations  in  the  size  of  the  smaller 

1  Thompson:  Archivfur  Physiologic,  isii.",,  p.  KM;  Bancroft:  American  Jou  mI  of  Physiology, 
1898,  i.  p.  177. 

'Cavazzani  ami  Manca:  Archives  italiennes  de  Biologie,  1895,  xxiv.  p.  '■'*'.'>. 


196  AN   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

vessels  distal  to  the  artery.  The  restrictions  are,  that  the  variations  in  the 
lateral  pressure  in  the  artery  are  indicative  of  changes  in  the  size  of  the  distal 
vessels  only  when  the  general  blood-pressure  remains  unaltered,  or  alters  in  a 
direction  opposite  to  the  change  in  the  artery  investigated.  An  example  will 
make  this  plain.  Dastre  and  Morat,  in  order  to  demonstrate  the  presence  of 
vaso-motor  fibres  for  the  hind  limb  in  the  sciatic  nerve,  connected  a  manometer 
with  the  central  end  of*  the  left  femoral  artery,  and  a  second  manometer  with 
the  peripheral  end  of  the  right  femoral  artery,  distal  to  the  origin  of  the  pro- 
funda femori-.  The  anastomoses  between  the  principal  branches  of  the  fem- 
oral artery  are  so  numerous  and  so  large  that  the  circulation  in  the  limb  can 
be  maintained  by  the  profunda  femoris  alone.  Dastre  and  Morat  could  there- 
fore compare  the  general  blood -pressure  with  the  blood-pressnre  in  the  right 
hind  limb.  On  stimulating  the  peripheral  end  of  the  right  sciatic  nerve,  the 
blood-pressure  rose  in  the  arteries  of  the  limb,  but  remained  stationary  in  the 
arteries  of  the  trunk,  connected  with  the  first  manometer  through  the  central 
end  of  the  left  femoral  artery.  The  rise  of  blood-pressnre  in  the  operated 
limb,  while  the  blood-pressnre  in  the  rest  of  the  body  remained  unchanged, 
proved  that  the  vessels  in  the  operated  limb  were  constricted. 

Many  investigators  have  studied  vaso-motor  phenomena  by  means  of  the 
plcthysmograph,  an  apparatus  invented  by  Mosso  for  recording  the  changes  in 
the  volume  of  the  extremities.  The  member,  the  vaso-motor  nerves  of  which 
are  to  be  studied,  is  placed  within  a  cylinder  rilled  with  water,  from  which  a 
tube  leads  to  a  recording  tambour.  An  increase  in  the  volume  of  the  member, 
such  as  would  be  brought  about  by  the  expansion  of  its  vessels,  causes  a  corre- 
sponding volume  of  water  to  enter  the  tambour  tube,  thus  raising  the  pressure 
in  the  tambour  and  forcing  its  lever  to  rise.  A  constriction  of  the  vessels,  on 
the  contrary,  causes  the  recording  lever  to  fall. 

In  addition  to  these  general  methods,  special  devices  have  been  employed 
in  the  researches  into  the  vaso-motor  nerves  of  the  brain. 

In  considering  the  observations  made  with  these  various  methods  it  will 
be  advisable  to  begin  with  the  differences  between  the  two  kinds  of  vaso-motor 
nerves. 

Differences  between  Vaso-constrictor  and  Vaso-dilator  Nerves. — The 
differences  between  vaso-constrictor  and  vaso-dilator  nerves  are  particularly 
interesting  for  the  reason  that  both  vaso-constrictor  and  vaso-dilator  fibres  are 
often   found  in  one  and  the  same  anatomical  nerve.     The  sciatic  nerve  is  a  ' 

g I  example  of  this.     By  taking  advantage  of  these  differences  the  investi- 

gator  may  determine  whether  one  or  both  kinds  of  fibres  are  present  in  an}' 
anatomical  nerve;  whereas,  without  this  knowledge,  the  effects  produced  by 
the  stimulation  of  the  one  mighl  be  wholly  masked  by  the  effects  produced  by 
the  stimulatioD  of  the  other. 

The  vaso-constrictors  are  less  easily  excited  than  the  vaso-dilators.  The 
Hinnltaneous  and  equal  stimulation  of  the  dilator  and  constrictor  nerves  going 
to  the  submaxillary  gland  causes  vaso-constriction,  dilatation  appearing  after 
tin   stimulation  ceases,  for  the  after-effect  of  excitation  is  of  shorter  duration 


CIRCULATION.  197 

with  the  constrictors  than  with  the  dilators.  Warming  increases  and  cooling 
diminishes  the  excitability  of  the  vaso-constrictors  to  a  greater  degree  than  is 
the  case  with  the  vaso-dilators.  Thus  if  the  hind  limb  of  an  animal  be 
warmed,  the  stimulation  of  the  sciatic  nerve  will  cause  vaso-constriction ; 
while  if  it  be  cooled  the  same  stimulation  will  cause  vaso-dilatation.1  Vaso- 
constrictors are  more  sensitive  to  rapidly  repeated  induction  shocks  (tetaniza- 
tion)  and  less  sensitive  to  single  induction  shocks  than  are  vaso-dilators.  Thus 
if  the  sciatic  nerve  is  stimulated  with  induction  shocks  of  the  same  strength,  it 
will  be  found  that  a  rapid  repetition  of  the  stimuli  will  give  vaso-constriction, 
while  with  single  shocks  at  intervals  of  five  seconds  vaso-dilatation  is  the  result. 
Vaso-constrictors  degenerate  more  rapidly  than  vaso-dilators  after  separation 
from  their  cells  of  origin.  The  stimulation  of  the  peripheral  end  of  the  frog's 
sciatic  nerve  immediately  after  section  causes  constriction.  Several  days  later 
the  same  stimulation  causes  vaso-dilatation,  the  constrictor  nerves  having  already 
degenerated  (see  Fig.  44,  B).  The  maximum  effect  of  stimulation  is  more 
quickly  reached  with  the  vaso-constrictor  than  with  the  vaso-dilator  nerves. 
There  is  also  a  difference  in  the  latent  period,  or  interval  between  stimulation 


A  B 

Fig.  44.— Curves  obtained  by  enclosing  the  hind  limb  of  a  cat  in  the  plethysmograph  and  stimu- 
lating the  peripheral  end  of  the  cut  sciatic  nerve  (Bowditch  and  Warren,  1886,  p.  447).    The  curves  read 

from  right  to  left.  In  each  case  the  vertical  lines  show  the  duration  of  the  stimulus — namely,  fifteen 
induction  shucks  per  second  during  twenty  seconds.  Curve  A  shows  the  contraction  of  the  vessels  pro- 
duced by  the  excitation  of  the  freshly-divided  nerve;  curve  B,  the  dilatation  produced  by  an  equal 
excitation  of  the  nerve  of  the  opposite  side  four  days  after  section,  the  vaso-constrictor  nerves  having 
degenerated  more  rapidly  than  the  vaso-dilators. 

and  response.  Bowditch  and  Warren  have  found  the  latent  period  of  the 
vaso-constrictor  fibres  iu  the  sciatic  to  be  about  1.5  seconds,  while  that  of  the 
vaso-dilators  is  3.5  seconds.  Finally,  the  two  sorts  of  nerves  have  been  said 
to  differ  in  the  manner  in  which  they  are  distributed.  The  vaso-constrictor 
nerves  leave  the  cord  as  medullated  fibres,  enter  the  sympathetic  chain  of  gan- 
glia and  end  in  terminal  branches  probably  in  contact  with  a  sympathetic 
ganglion-cell.  The  constrictor  impulse  is  forwarded  to  the  vessel  by  a 
process  of  this  cell,  either  directly  or  by  means  <>f  -till  other  sympathetic 
ganglion-cells.  The  vaso-dilator  fibre,  on  the  contrary,  was  thought  to  run 
directly  from  the  cord  to  the  blood-vessel  ;  but  recent  investigations  make  it 
probable  that  all  spinal  vaso-motor  fibres  end  in  sympathetic  ganglia. 

Origin  and  Course. — The  vaso-motor  nerves  the  general   properties  of 
which  have  just  been  studied  are  axis-cylinder  processes  of  sympathetic  gan- 
glion-cells.    They  follow,  fir  a  time  at  least,  the  course  of  the  corresponding 
'Howell,  Budgett,  and  Leonard:  Journal  of  Physiology,  L894,  \\i.  p.  298. 


198  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

spinal  nerve.  According  to  Langley,1  they  do  not  differ  from  the  pilo-motor 
and  secretory  nerves  except  in  the  nature  of  the  structure  in  which  they  termi- 
nate. They  are  not  interrupted  by  other  nerve-cells  on  their  course.  The 
action  of  the  sympathetic  vaso-motor  cells  is  influenced  by  the  vaso-motor 
cells  of  the  spinal  cord  and  bulb.  These  are  probably  small  cells  situated  at 
various  levels  in  the  anterior  horn  and  lateral  gray  substance.  Their  axis- 
cylinder  processes  leave  the  cerebro-spinal  axis  by  the  anterior  roots2  of 
certain  spinal  and  by  certain  cranial  nerves,  and  enter  sympathetic  ganglia, 
where  they  end  in  terminal  twigs  probably  in  contact  with  the  sympathetic 
vaso-motor  cells.  The  vaso-motor  cells  lying  at  various  levels  in  the  cerebro- 
spinal axis  are  in  turn  largely  controlled  by  an  association  of  cells  situated  in 
the  bulb  and  termed  the  vaso-motor  centre.  The  neuraxons  (axis-cylinder 
processes)  of  the  cells  composing  this  "centre"  pass  in  part  to  the  nuclei  of 
certain  cranial  nerves  and  in  part  down  the  lateral  columns  of  the  cord,  to 
end  in  contact  with  the  spinal  vaso-motor  cells.  The  vaso-motor  apparatus 
consists,  then,  of  three  classes  of  nerve-cells.3  The  cell-bodies  of  the  first  class 
lie  in  sympathetic  ganglia,  their  neuraxons  passiug  directly  to  the  smooth  mus- 
cle- in  the  walls  of  the  vessels;  the  second  are  situated  at  different  levels  in 
the  cerebro-spinal  axis,  their  neuraxons  passing-  thence  to  the  sympathetic  gan- 
glia by  way  of  the  spinal  and  cranial  nerves;  and  the  third  are  placed  in  the 
bulb  and  control  the  second  through  intraspinal  and  intracranial  paths.  The 
nerve-cell  of  the  first  class  lies  wholly  without  the  cerebro-spinal  axis,  the  third 
wholly  within  it,  while  the  second  is  partly  within  and  partly  without,  and 
binds  together  the  remaining  two. 

The  evidence  for  the  existence  of  these  vaso-motor  nerve-cells  must  now 
be  considered.  We  shall  begin  with  those  of  the  third  class,  constituting  the 
so-called  bulbar  vaso-motor  centre. 

Bulbar  Vaso-motor  Centre. — The  section  of  the  spinal  cord  near  its 
junction  with  the  bulb  is  followed  by  the  general  dilatation  of  the  blood- 
vessels  of  the  trunk  and  limbs.  The  dilated  vessels  are  again  constricted 
when  the  severed  fibres  in  the  spinal  cord  are  artificially  stimulated.  Hence 
the  section  caused  the  dilatation  by  interrupting  the  vaso-constrictor  impulses 
passing  from  the  bulb  to  parts  below.  The  position  of  the  bulbar  vaso- 
constrictor centre  has  been  determined  by  Owsjannikow  and  Dittmar.  The 
former  observer  divided  the  bulb  transversely  at  various  levels.  When  the 
section  fell  immediately  caudal  to  the  corpora  quadrigeraina,  only  a  slight 
temporary  rise  in  blood-pressure  was  observed.  When,  however,  the  section 
fell  a  millimeter  or  two  nearer  the  cord,  a  considerable  and  permanent  fall  in 
the  blood-pressure  was  noted.  Further  lowering  was  seen  as  the  sections 
were  carried  still  farther  toward  the  spinal  cord,  until  at  length,  about  four 
millimeters  from   the  corpora  quadrigemina,  no  further  fall   took  place.     The 

'  Langley      '  f  Physiology,  1894,  xvii.  p.  314. 

'Compare  Werziloff:   Centralblalt fur  Physiologi' ,  ISO*),  x.  p.  194. 
I'.\  "nerve-cells"  is  meant  the  cell-body  with  nil  its  processes,  namely,  the  neuraxon,  or 
axis-cylinder  process,  and  the  dendrites,  <>r  protoplasmic  processes. 


CIRCULA  TION.  199 

ana  from  which  the  vaso-constrictor  nerves  receive  a  constant  excitation 
extends,  therefore,  in  the  rabbit,  over  about  three  millimeters  of  the  bulb  not 
far  from  the  corpora  quadrigemina.  Two  years  after  this  investigation  I>itt- 
mar  added  to  the  observations  of  Owsjannikow  the  fact  that  the  vaso-con- 
strictor centre  is  bilateral,  lying  in  the  anterior  part  of  the  lateral  columns  on 
both  sides  of  the  median  line.  At  this  site  is  found  a  group  of  ganglion-cells 
known  as  the  antero-lateral  nucleus  of  Clarke.  It  is  possible,  though  far 
from  certain,  that  these  are  the  cells  of  the  vaso-constrictor  centre. 

The  vaso-constrictor  centre  in  the  bulb  is  always  in  a  state  of  action,  or 
"tonic"  excitation,  as  is  shown  by  the  dilatation  of  the  vessels  when  deprived 
of  their  constrictor  impulses  through  the  section  of  the  spinal  cord. 

It  is  not  definitely  known  whether  a  vaso-dilator  centre  is  present  in  the 
bulb. 

Spinal  Centres. — A  complete  demonstration  of  the  existence  of  vaso-motor 
centres  in  the  spinal  cord,  first  suggested  by  Marshall  Hall,  was  made  by  Goltz 
and  Freusberg  in  their  experiments  on  dogs  which  had  been  kept  alive  after 
the  division  of  the  spinal  cord  at  the  junction  of  the  dorsal  and  the  lumbar 
regions.  This  operation  cuts  off  both  sensory  and  motor  communication 
between  the  parts  lying  above  and  below  the  plane  of  section,  and  divides  the 
animal  physiologically  into  a  fore  dog  and  a  hind  dog,  to  use  the  author's 
expression.  The  investigator  can  now  explore  the  lumbar  cord  unvexed  by 
cerebral  impulses.  A  great  number  of  motor  reflexes  formerly  thought  to  have 
their  centres  exclusively  in  the  brain  are  by  this  means  found  to  take  place 
in  the  absence  of  the  brain.1  That  vaso-motor  reflexes  were  among  them  was 
discovered  by  accident.  It  was  noticed  that  the  mechanical  stimulation  of  the 
skin  of  the  abdomen  and  penis  while  the  animal  was  being  washed  provoked 
erection,  which,  as  Eckhard  had  discovered  some  years  before,  is  a  reflex  action 
due  to  the  dilatation  of  the  arteries  of  the  penis  through  impulses  conveyed  by 
the  nervi  erigentes.  Pressure  on  the  bladder,  or  the  walls  of  the  rectum,  also 
had  this  effect.  After  the  destruction  of  the  lumbar  cord  this  reflex  was  no 
longer  possible.  The  vessels  of  the  hind  limb  are  also  connected  with  vaso- 
motor cells  in  the  lumbar  cord.  Soon  after  the  section  of  the  cord  in  the  dorsal 
region  the  hind  paws  are  observed  to  be  warmer  than  the  fore  paws,  and  the 
arteries  of  the  hind  limb  are  seen  to  beat  more  strongly.  This  is  the  resuli  of 
cutting  off  the  vaso-constrictor  impulses  from  the  bulbar  centre  to  the  vessels 
in  question.  If  the  animal  survives  a  considerable  time  the  hind  paws  will 
be  observed  to  grow  cooler  from  day  to  day  until  they  are  again  no  warmer 
than  the  fore  paws.  Destruction  of  the  lumbar  cord  now  causes  the  tempera- 
ture of  the  hind  limbs  to  rise  again. 

The  conclusion  drawn  from  these  observations  is  that  vaso-motor  cells  are 
present  in  the  spinal  cord.  It  is  probable  that  they  are  normally  subordinated 
to  the  bulbar  nerve-cells  and  requires  certain  time  after  separation  from  the 
bulb  in  order  to  develop  their   previously  rudimentary   powers.      Hence  the 

1  Later  experiments  by  <  roltz  \w\  Ewald,  showing  the  degree  of  independence  of  the  spinal 
cord  possessed  by  sympathetic  vaso-motor  neurons,  will  presently  be  cited. 


200  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

interval  of  many  days  between  the  section  and  the  return  of  arterial  tone  in  areas 
distal  to  the  section.  It  has  been  suggested  that  during  this  period  the  power 
of  the  spinal  nerve-cell  is  inhibited  by  impulses  proceeding  from  the  cut  sur- 
face of  the  cord,1  but  this  long  inhibition  is  questionable  in  view  of  the  fact 
that  transverse  section  of  the  cord  in  rabbits  and  dogs  does  not  inhibit  the 
phrenic  nuclei.2 

The  spinal  nerve-cell  take-  part  in  vaso-motor  reflexes.  Thus  the  stimu- 
lation of  the  central  end  of  the  brachial  nerves  after  section  of  the  spinal  cord 
at  the  third  vertebra  causes  a  dilatation  of  the  vessels  of  the  fore  limb.  The 
stimulation  of  the  central  end  of  the  sciatic  nerve  after  the  division  of  the 
spinal  cord  causes  a  general  rise  of  blood-pressure  indicating  the  constriction 
of  many  vessels.  The  sensory  stimulation  of  one  hind  limb  may  cause  reflexly 
a  narrowing  of  the  vessels  in  the  other,  after  the  spinal  cord  is  severed  in  the 
mid-thoracic  region.  In  asphyxia,  after  the  separation  of  the  cord  from  the 
brain,  vascular  constriction  is  produced  reflexly  through  the  spinal  centres. 
This  constriction  is  not  observed  if  the  cord  is  previously  destroyed.  Goltz 
and  Ewald  find  that  the  tonic  constriction  of  the  vessels  of  the  hind  limbs 
returns  after  the  extirpation  of  the  lower  part  of  the  spinal  cord. 

Sympathetic  Vaso-motor  Centres. — Gley  3  finds  that  after  the  destruc- 
tion of  both  bulbar  and  spinal  centres  some  degree  of  vascular  tone  is  still 
maintained.  The  extraordinary  experiments  of  Goltz  and  Ewald  place  this 
fact  beyond  question.  These  physiologists  remove  the  lower  part  of  the  spinal 
cord  completely,  taking  away  80  millimeters  or  more.  For  a  few  days  after 
the  operation  the  hind  limbs  are  hot  and  red,  from  dilatation  of  their  blood- 
vessels. Soon,  however,  the  hind  limbs  become  as  cool,  and  sometimes  even 
cooler,  than  the  fore  limbs,  their  arterial  tonus  being  re-established  and  main- 
tained without  the  help  of  the  spinal  cord. 

The  sympathetic  ganglia  are  probably  also  centres  of  reflex  vaso-motor 
action.  The  fact  that  these  ganglia  act  as  centres  for  other  motor  reflexes 
would  itself  suggest  this  possibility.  Evidence  of  the  vaso-motor  reflex 
function  of  the  first  thoracic  ganglion  has  been  offered  recently  by  Francois- 
Franck.4  The  two  branches  composing  the  annulus  of  Vieussens  contain  both 
afferent  and  efferent  fibres.  If  one  of  the  branches  is  cut, and  the  end  in  con- 
nection with  the  first  thoracic  ganglion  is  stimulated,  the  ganglion  having  been 
6  sparated  from  the  spinal  cord  by  the  section  of  the  communicating  branches, 
a  constriction  of  the  vessels  of  the  ear,  the  submaxillary  gland,  and  the  nasal 
mucous  membrane  may  be  observed. 

This  evidence,  together  with  the  probability  that  the  neuraxons  of  all  the 
spinal  vaso-motor  cells  end  in  sympathetic  ganglia,5  makes  it  fairly  credible 
that  the  sympathetic  vaso-motor  nerve-cell  possesses  central  functions. 

1  Goltz  and  Ewald:  Arrhiv  fiir  die  gesammte  Physiologie,  1896,  lxiii.  p.  397. 

'Porter:  Journal 'of  Physiology,  1895,  xvii.  p.  459. 

3 Gley:  Archives  de  Physiologic,  1894,  p.  704. 

*  Franck  :  Archives  de  Physiologie,  1894,  p.  721. 

5 See  the  statement  of  Langley's  results  with  the  nicotin  method  on  page  '208. 


CIR  CULA  TION.  20 1 

There  has  been  much  discussion  over  the  meaning  of  the  rhythmic  con- 
tractions observed  in  certain  blood-vessels  apparently  independent  of  the  cen- 
tral nervous  system.1  The  median  artery  of  the  rabbit's  ear,  the  arteria 
saphena  in  the  same  animal,  and  the  vessels  in  the  frog's  web  and  frog's  mes- 
entery, slowly  contract  and  relax.  This  rhythmic  contraction  is  easily  seen  in 
the  ear  of  a  white  rabbit.  The  movements  are  possibly  of  purely  muscular 
origin,  but  are  more  probably  the  result  of  periodical  discharges  by  vaso-motor 
nerve-cells. 

Rhythmical  variations  in  the  tonus  of  the  vaso-constrictor  centres  are  often 
held  to  explain  the  oscillations  seen  in  the  blood-pressure  curve  after  the 
influence  of  thoracic  aspiration  has  been  eliminated  by  opening  the  chest  and 
cutting  the  vagus  nerves.  These  oscillations  are  of  two  sorts.  In  the  one, 
the  blood-pressure  sinks  with  every  inspiration  and  rises  with  every  expiration, 
though  the  rise  and  fall  are  not  precisely  synchronous  with  the  respiratory 
movements ;  in  the  other,  the  so-called  Traube-Hering  waves,  the  oscillations 
embrace  several  respirations.  It  has  also  been  suggested  that  these  phenomena 
are  due  to  periodical  changes  in  the  respiratory  centre  affecting  the  vaso-con- 
strictor centre  by  "  irradiation." 

Vaso-motor  Reflexes. — The  vaso-motor  nerves  can  be  excited  reflexly  by 
afferent  impulses  conveyed  either  from  the  blood-vessels  themselves  or  from 
the  end-organs  of  sensory  nerves  in  general.  The  existence  of  reflexes  from 
the  blood-vessels  may  be  shown  by  Heger's  experiment.  Heger  observed  a 
rise  of  general  blood-pressure  with  a  subsequent  fall,  and  at  times  a  primary 
fall,  after  the  injection  of  nitrate  of  silver  into  the  peripheral  end  of  the  crural 
artery  of  a  rabbit.  The  limb,  with  the  exception  of  the  sciatic  nerve,  was 
severed  from  the  trunk.  The  quantity  injected  was  so  small  that  it  probably 
was  decomposed  before  passing  the  capillaries  or  escaping  from  the  blood- 
vessels. Thus  the  effect  exerted  by  the  nitrate  of  silver  on  the  general  blood- 
pressure  was  probably  caused  by  afferent  impulses  set  up  in  the  blood-vessels 
themselves  and  transmitted  through  the  sciatic  nerve  to  the  vaso-motor  cen- 
tres. Vaso-motor  reflexes  are,  however,  much  more  commonly  produced 
by  the  stimulation  of  sensory  nerves  other  than  those  present  in  the  blood- 
vessels. 

The  reflex  constriction  or  dilatation  2  appears  usually  in  the  vascular  area 
from  which  the  afferent  impulses  arise.  For  example,  the  stimulation  of  the 
central  end  of  the  posterior  auricular  nerve  in  the  rabbit  causes  a  passing  con- 
striction followed  by  dilatation,  or  a  primary  dilatation  often  followed  by 
constriction  of  the  vessels  in  the  ear.  The  stimulation  of  the  nervi  erigentes 
causes  dilatation  of  the  vessels  of  the  penis.  Gaskell  found  thai  tin1  vessels 
of  the  mylo-hyoid  muscle  widened  on  stimulating  the  mucous  membrane  at 
the  entrance  of  the  glottis. 

1  Franck  :  Archives  de  Physiologic,  1803,  p.  729;  Lui:  Archives  ilaliennes  de  Biologic,  1894,  xxi. 
p.  416  ;  Goltz  and  Ewald  :   Archivf&r  die  gesammte  Physiologic,  1890,  lxiii.  p.  396. 
'z  Hegglin  :  Zeitschrifl  filr  klinische  Medicin,  1894,  xxvi.  p.  25. 


202  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

The  vascular  reflex  '  may  appear  in  a  part  associated  in  function  with  the 
sensory  surface  stimulated.  Thus  the  stimulation  of  the  tongue  causes  dilata- 
tion of  the  blood-vessels  in  the  submaxillary  gland.  Frequently  the  vascular 
reflex  is  seen  on  both  ^i«lts  of  the  body.  The  stimulation  of  the  mucous 
membrane  on  one  side  of  the  nose  may  cause  vascular  dilatation  in  the  whole 
head;  the  effect  in  this  case  is  usually  more  marked  on  the  side  stimulated. 
The  vessels  of  one  hand  contract  when  the  other  hand  is  put  in  cold  water. 
Sometimes  distant  and  apparently  unrelated  parts  are  affected.  Vulpian 
noticed  that  the  stimulation  of  the  central  end  of  the  sciatic  caused  the  vessels 
of  the  tongue  to  contract.2 

The  vascular  changes  produced  reflexly  in  the  splanchnic  area  are  of 
especial  importance  because  of  the  great  number  of  vessels  innervated  through 
these  nerves  and  the  great  changes  in  the  blood-pressure  that  can  follow  dilata- 
tion or  constriction  on  so  large  a  scale. 

There  is  in  some  degree  an  inverse  relation  between  the  vessels  of  the  skin 
and  deeper  parts  on  reflex  stimulation  of  the  vaso-motor  centres.  The  super- 
ficial vessels  are  often  dilated  while  those  of  deeper  parts  are  constricted.3 
Thus  the  stimulation  of  the  central  end  of  the  sciatic  nerve  may  cause  a  dilata- 
tion of  the  vessels  of  the  lips,  hand  in  hand  with  a  rise  in  general  blood-pres- 
sure.4 Exposing  a  loop  of  intestine  dilates  the  intestinal  vessels  in  the  rabbit, 
but  constricts  those  of  the  ear.  In  asphyxia,  the  superficial  vessels  of  the  ear, 
face,  and  extremities  dilate,  while  the  vessels  of  the  intestine,  spleen,  kidneys 
and  uterus  are  constricted. 

Relation  of  Cerebrum  to  Vaso-motor  Centres. — A  rise  of  general  blood- 
pressure  has  been  produced  by  the  stimulation  of  different  regions  of  the  cortex 
and  of  various  other  parts  of  the  brain  ;  for  example,  the  crura  cerebri  and 
corpora  quadrigemina.  Yaso-dilatation  has  also  been  observed.  The  motor 
area  of  the  cortex  especially  seems  closely  connected  with  the  bulbar  vaso- 
motor centres.  There  is,  however,  no  conclusive  evidence  that  special  vaso- 
motor centres  exist  in  the  brain  aside  from  the  bulbar  centres  already  described. 
At  present  the  safer  view  is  that  the  changes  in  blood-pressure  called  forth  by 
the  stimulation  of  various  parts  of  the  brain  are  reflex  actions,  the  afferent  im- 
pulse starting  in  the  brain  as  it  might  in  any  other  tissue  peripheral  to  the 
vaso-motor  centres. 

Pressor  and  Depressor  Fibres. — The  stimulation  of  the  same  afferent 
nerve  sometimes  causes  reflex  dilation  of  the  vessels  of  a  part,  instead  of  the 
more  usual  reflex  constriction.  Two  explanations  of  this  fact  have  been  sug- 
gested. The  first  assumes  that  the  condition  of  the  vaso-motor  centre  varies  in 
such  a  way  that  the  same  stimuli  might  produce  contrary  effects,  depending 
on  the  relation  between  the  time  of  stimulation  and  the  condition  of  the  centre. 

1  The  general  arrangement  of  the  matter  in  this  paragraph  is  that  given  hy  Tigerstedt,  Der 

mf  1893,  p.  519. 
*  Compare  Sergejew :   Gentralblatt  fur  die  medicinische  Wissemehaft,  1894,  ]>.  162. 
s Wertheimer :  Gomptes  rendus,  1893,  cxvi.  p.  595;  rlallion  and  Franck:  Archives de  Physi- 
olo'ii ,  1896,  p.  502;   Bayliss  and  Bradford:  Journal  of  Physiology,  1SU4,  xvi.  p.  17. 
i  [sergin:   Arehivfur  Physiologic,  L894,  p.  448. 


CIRCULATION.  203 

The  second  assumes  the  existence  of  special  reflex  constrictor  or  "pressor" 
fibres,  and  reflex  dilator  or  "depressor"  fibres.  The  existence  of  at  least  one 
depressor  nerve  is  beyond  question,  namely  the  cardiac  depressor  nerve,  which 
it  will  be  remembered  runs  from  the  heart  to  the  bulb  and  when  stimulated 
causes  a  dilatation  of  the  splanchnic  and  other  vessels  reflexly  through  the 
bulbar  vaso-motor  centre.  Evidence  of  other  reflex  vaso-dilator  nerves  and  of 
reflex  vaso-constrictor  fibres  as  well  has  been  offered  by  Latschenberger  and 
Deahna,  Howell,1  and  others.  Howell,  for  example,  has  found  that  if  a  part  of 
the  sciatic  nerve  is  cooled  to  near  0°  C.  and  the  central  end  stimulated  periph- 
erally to  this  part,  the  blood-pressure  falls,  instead  of  rising,  as  it  does  when 
the  nerve  is  stimulated  without  previous  cooling.  Howell's  experiments  have 
been  recently  extended  by  Hunt,  who  finds  that  the  stimulation  of  the  sciatic 
during  its  regeneration  after  section  gives  at  first  vaso-dilatation  only,  but  when 
regeneration  has  progressed  still  further,  vaso-constriction  is  secured.  These 
results  point  to  the  existence  of  both  pressor  and  depressor  fibres,  the  latter 
being  the  first  to  regenerate  after  section.  A  reflex  fall  in  blood-pressure  is 
also  produced  by  stimulating  various  mixed  nerves  with  weak  currents  and 
bv  the  mechanical  stimulation  of  the  nerve-endings  in  muscle.  The  fall  is 
more  readily  obtained  when  the  animal  is  under  ether,  chloroform,  or  chloral, 
less  readily  under  curare. 

Topography. — We  pass  now  to  the  vaso-motor  nerves  of  various  regions. 

Brain.2 — The  study  of  the  innervation  of  the  intracranial  vessels  is  ren- 
dered exceptionally  difficult  by  the  fact  that  the  brain  and  its  blood-vessels  are 
placed  in  a  closed  cavity  surrounded  by  walls  of  unyielding  bone.  The  funda- 
mental difference  created  by  this  arrangement  between  the  vascular  phenomena 
of  the  brain  and  those  of  other  organs  was  recognized  in  part  at  least  by 
the  younger  Monro  as  long  ago  as  1783.  Monro  declared  that  the  quantity 
of  blood  within  the  cranium  is  almost  invariable,  "  for,  being  enclosed  in  a 
case  of  bone,  the  blood  must  be  continually  flowing  out  of  the  veins  that  room 
may  be  given  to  the  blood  which  is  entering  by  the  arteries, — as  the  substance 
of  the  brain,  like  that  of  the  other  solids  of  our  body,  is  nearly  incompress- 
ible." Further  differences  between  the  circulation  in  the  brain  and  in  other 
organs  are  introdueed  by  the  presence  of  the  cerebrospinal  fluid  in  the  ventri- 
cles and  in  the  arachnoidal  spaces  at  the  base  of  the  brain.  This  fluid  may  pass 
out  into  the  spinal  canal  and  thus  leave  room  for  an  increase  in  the  amount 
of  blood  in  the  cranium.  Finally,  a  rise  of  pressure  in  the  arteries  too  great 
to  be  compensated  by  the  outflow  of  cerebro-spinal  fluid  may  lead  to  com- 
pression of  the  venous  sinuses  and  a  decided  change  in  the  relative  distri- 
bution of  the  blood  in  the  arteries,  capillaries  and  vein — conditions  which  are 
not  present  in  extracranial  tissues.  It  is  evident,  therefore,  thai  the  methods 
employed  in  the  search  for  vaso-motor  nerves  within  the  cranium  must   take 

'Howell,  Budgett,  and  Leonard  Journal  of  Physiology,  1894,  xvi.  p.  .'<U>:  Bayliss:  Ibid., 
1893,  xiv.  p.  317  ;   Bradford  and  Dean:   Ibid,,  1894,  xvi.  p.  67 ;   Hunt:   Ibid.,  1895,  xviii.  p.  381. 

1  Cavazzani:  Archives  italiennes  de  Biologie,  1893,  xviii.  p.  54,  lix.  p.  214;  Bayliss  and  Hill: 
Journal  of  Physiology,  1895,  xviii.  p.  334;  Gulland:   Ibid.,  p.  361. 


204  AN   AMERICAN    TEXT- BOOK   OF  PHYSIOLOGY. 

into  account  many  sources  of  error  that  are  absent  in  vaso-motor  studies  of 
other  regions.  It  is,  indeed,  probable  that  incompleteness  of  method  will  go 
far  Toward  explaining  the  disagreement  of  authors  as  to  the  presence  of  vaso- 
motor nerves  in  the  brain.  According  to  Bayliss  and  Hill,  who  have  recently 
studied  this  subject,  it  is  necessary  to  record  simultaneously  the  arterial 
pressure,  the  general  venous  pressure,  the  intracranial  pressure  and  the  cerebral 
venous  pressure,  the  cranium  as  in  the  normal  condition  being  kept  a  closed 
cavity.  In  their  experiments,  "a  cannula  was  placed  in  the  central  end  of  the 
carotid  artery.  A  second  long  cannula  was  passed  down  the  external  jugular 
vein,  and  on  the  same  side,  into  the  right  auricle.  The  torcular  Herophili  was 
trephined,  and  a  third  cannula,  this  time  of  brass,  was  screwed  into  the  hole 
thus  made."  The  intracranial  pressure  was  recorded  by  a  cannula  connected 
through  another  trephine-hole  with  the  subdural  space. 

Bayliss  and  Hill  could  find  no  evidence  of  the  existence  of  cerebral  vaso- 
motor nerves.  The  cerebral  circulation,  according  to  them,  passively  follows 
the  changes  in  the  general  arterial  and  venous  pressure.  Gulland  has  examined 
the  cerebral  vessels  by  the  Golgi,  Ehrlich,  and  other  methods,  to  determine 
whether  nerve-fibres  could  be  demonstrated  in  them.  None  were  found.  It 
is  probable  that  the  blood-supply  to  the  brain  is  regnlated  through  the  bulbar 
va-n-eonstrictor  centre.  Anaemia  or  asphyxia  of  the  brain  stimulates  the  cells 
composing  this  centre,  vascular  constriction  of  many  vessels  follows,  and  more 
blood  enters  the  cranial  cavity.  The  vessels  of  the  splanchnic  area  play  a 
chief  part  in  this  regulative  process.1  Their  importance  to  the  circulation  in 
the  brain  is  shown  by  the  fatal  effect  of  the  section  of  the  splanchnic  nerves 
in  the  rabbit.  On  placing  the  animal  on  its  feet,  so  much  blood  flows 
into  the  relaxed  abdominal  vessels  that  death  may  follow  from  anaemia  of  the 
brain. 

Vaso-motor  Nerves  of  Head. — The  cervical  sympathetic  contains  vaso-con- 
strictor  fibres  for  the  corresponding  side  of  the  face,  the  eye,  ear,  salivary 
glands  and  tongue,  and  possibly  the  brain.  The  spinal  vaso-constrictor 
fibres  tor  the  vessels  of  the  head  in  the  cat  and  dog  leave  the  cord  in  the 
first  five  thoracic  nerves  ;  in  the  rabbit,  in  the  second  to  eighth  thoracic,  seven 
in  all. 

Vaso-dilator  fibres  for  the  face  and  month  have  been  found  in  the  cervical 
sympathetic  by  Dastre  and  Morat,  leaving  the  cord  in  the  second  to  tilth 
dorsal  nerves,  and  uniting  (at  least  for  the  most  part)  with  the  trigeminus  by 
passing,  according  to  Morat,  from  the  superior  cervical  >yinpathetic  ganglion 
to  the  ganglion  of  Gasser.  Other  dilator  fibres  for  the  skin  and  mucous 
membrane  of  the  face  and  mouth  arise  apparently  in  the  trigeminus,  for  the 
stimulation  of  this  nerve  between  the  brain  and  Gasser's  ganglion  causes  dila- 
tation of  the  vessels  of  the  face,2  and  in  the  nerve  of  Wrisberg. 

The  vaso-motor  nerves  of  the  tongue  have  been  recently  studied  by  Isergin.3 

1  Wertheiiner :  Archives  de  Physiologic,  1893,  p.  297. 

2  Langley:  Philosophical  Transactions,  1892,  j).  104  ;  Piotrowsky :  Ccntralblatt  fiir  Physiologic 
1892,  vi.  p.  464.  3  Isergin  :  Archie  fiir  Physiologic,  1894,  p.  441. 


CIRCULATION.  205 

The  lingual  and  the  glossopharyngeal  nerves  are  recognized  by  all  authors  as 
dilators  of  the  lingual  vessels.  The  sympathetic  and  the  hypoglossus  contain 
constrictor  fibres  for  the  tongue.  It  is  possible  that  the  lingual  contains  also 
a  small  number  of  constrictor  fibres.  Most  if  not  all  these  vasomotor  fibres 
arise  in  the  sympathetic  and  reach  the  above-mentioned  nerves  by  way  of  the 
superior  cervical  ganglion.  They  degenerate  in  from  three  to  five  weeks  after 
the  extirpation  of  the  ganglion. 

Morat  and  Doyon  cut  the  cervical  sympathetic  in  a  curarized  rabbit  and 
examined  the  retinal  arteries  with  the  ophthalmoscope.  They  were  found 
dilated.  The  excitation  of  the  cervical  sympathetic  caused  constriction,  the 
excitation  of  the  thoracic  sympathetic  dilatation  of  these  vessels.  The  retinal 
fibres  leave  the  sympathetic  at  the  superior  cervical  ganglion  and  pass  along 
the  communicating  ramus  to  the  ganglion  of  Gasser,  whence  they  reach  the 
eye  through  the  ophthalmic  branch  of  the  fifth  nerve,  the  gray  root  of  the 
ophthalmic  ganglion,  and  the  ciliary  nerves.  Most,  or  all,  of  the  fibres  for 
the  anterior  part  of  the  eye  are  found  in  the  fifth  nerve. 

Lungs. — The  methods  ordinarily  employed  for  the  demonstration  of  vaso- 
motor nerves  cannot  without  danger  be  used  in  the  studv  of  the  innervation 


Fig.  45.— The  excitation  of  the  central  end  of  the  inguinal  branch  of  the  crural  (sciatic)  nerve  causes 
a  rise  in  the  aortic  pressure  (Pr  A.F.),  a  rise  in  the  pressure  in  the  pulmonary  artery  (Pr.A.P.)  of  10  to  16 
mm  Hg,  accompanied  by  a  falling  pressure  in  the  left  auricle  (Pr.O.G.)  (Franck,  1896,  p  184).  The  rise 
of  pressure  in  the  pulmonary  artery,  together  with  the  fall  in  the  left  auricle,  demonstrate,  according 
to  Franck,  a  constriction  of  the  pulmonary  vessels. 

of  the  pulmonary  vessels.1  A  fall  in  the  blood- pressure  in  the  pulmonary 
artery,  for  example,  produced  by  stimulating  any  nerve  cannot  be  taken  as 
final  evidence  that  the  stimulation  caused  the  constriction  of  the  pulmonary 
vessels.  The  lesser  circulation  is  so  connected  that  changes  in  the  calibre  of 
the  vessels  of  a  distant  part,  the  liver  for  example,  may  alter  the  quantity  of 
blood  in  the  lungs.  The  method  of  Cavazzani  avoid-  these  difficulties. 
Cavazzani  establishes  an  artificial  circulation  through   one   lobe  of'  a  lung  in 

1  Doyon  :  Archives  de  Physiologic,  1893,  p.  L0]  ;  Henriques :  SkaTidinavisches  Archiv  fur  Physi- 
ologic, 189.3,  iv.  p.  2'2\) ;  Bradford  and  Dean  :  Journal,  of  Physiology,  L894,  xvi.  p.  34  ;  Franck: 
Archives  de  Physiologie,  L896,  |>.  L78. 


206  AN    AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

a  living  animal,  and  measures  t h< -  outflow  per  unit  of  time.  An  increase  iu 
the  outflow  means  a  dilatation  of  the  vessels,  diminution  means  constriction. 
He  finds  thai  the  outflow  diminishes  in  the  rabbit  when  the  vagus  is  stimulated 
in  the  neck,  and  increases  when  the  cervical  sympathetic  is  stimulated.  Franck 
measures  the  pressure  simultaneously  in  the  pulmonary  artery  and  left  auricle, 
a  method  apparently  also  trustworthy.  The  stimulation  of  the  inner  surface 
of  the  aorta  causes  a  rise  of  pressure  in  the  pulmonary  artery  and  a  simul- 
taneous fall  in  the  left  auricle,  indicating,  according  to  Franck,  the  vaso-con- 
strictor  power  of  the  sympathetic  nerve  over  the  pulmonary  vessels.  A  reflex 
constriction  is  also  produced  by  the  stimulation  of  the  central  end  of  a  branch 
of  the  sciatic,  intercostal,  abdominal  pneumogastric,  and  abdominal  sympa- 
thetic nerves  (see   Fig.  45). 

Heart. — Vaso-motor  fibres  lor  the  coronary  arteries  of  the  heart  have  been 
described.1 

Intestines.'2 — The  mesenteric  vessels  receive  vaso-constrictor  fibres  from  the 
sympathetic  chiefly  through  the  splanchnic  nerve.  The  vaso-constrictors  of 
the  jejunum,  as  a  rule,  begin  to  be  found  in  the  rami  of  the  fifth  dorsal  nerves ; 
a  little  lower  down,  those  for  the  ileum  come  off;  and  still  lower  down,  those 
for  the  colon  ;  none  arise  below  the  second  lumbar  pair.  According  to  Hal- 
lion  and  Franck,  vaso-dilator  fibres  are  present  in  the  same  sympathetic  nerves 
that  contain  vaso-constrictors.  The  dilator  fibres  are  most  abundant  or  most 
powerful  in  the  rami  of  the  last  three  dorsal  and  first  two  lumbar  nerves. 
There  is  some  evidence  of  the  presence  of  vaso-dilator  fibres  in  the  vagus. 
The  excitation  of  the  vaso-constrictor  centres  by  the  blood  in  asphyxia  pro- 
duces constriction  of  the  abdominal  vessels.  The  vaso-dilator  as  well  as  the 
vaso-constrictor  fibres  of  the  splanchnic  probably  end  in  the  solar  and  renal 
plexuses. 

Liver. — Cavazzani  and  Manca  3  have  recently  attempted  to  show  the  pres- 
ence of  vaso-motor  fibres  in  the  liver.  Their  method  consists  in  passing  warm 
normal  saline  solution  from  a  Mariotte's  flask  at  a  pressure  of  8  to  10  milli- 
meters Hg  through  the  hepatic  branches  of  the  portal  vein  and  measuring 
the  outflow  in  a  unit  of  time  from  the  ascending  vena  cava.  On  stimulating 
the  splanchnic  nerve  they  observed  that  the  outflow  was  usually  diminished 
though  sometimes  increased,  indicating  perhaps  that  the  splanchnics  contain 
both  vaso-constrictor  and  vaso-dilator  fibres  for  the  hepatic  branches  of  the 
portal  vein.  The  vagus  appeared  to  contain  vaso-dilator  fibres.  Further 
studies  are  necessary,  however,  before  pronouncing  definitely  upon  these 
questions. 

'Porter:   Boston  Medical  and  Surgical  Journal,  1896,  ex  xxiv.  39 ;  Porter  and  Beyer:  Ameri- 

Journal  of  Physiol  xj  ij,  1900,  iii.  j>.  xxiv.  ;  Maass  :  Archiv  fiir  du  :,<  ammte  Physialogie,  1899, 
Ixxiv.  p.  281. 

-  rlallion  ami  Franck  :  Archives  de  Physiologie,  1896,  xxviii.  pp.  478,  193  ;  Bunch  :  Journal  <>f 
Physiology,  1899,  xxiv.  p.  72. 

'<  avazzani  and  Manca:  Archives  italiennes  <l>'  Biologic,  L895,  xxiv.  p.  :;:;;  Franpois-Franck 
and  Hallion:   Archives  d   Physiologie,  L896,  pp.  908,  923;   1897,  pp.  134,   148. 


CIRCULATION.  207 

Kidney} — The  vasomotor  nerves  of  the  kidney  leave  the  cord  from  the 
sixth  dorsal  to  the  second  lumbar  nerve.  In  the  dog,  most  of  the  renal  vaso- 
motor fibres  are  found  in  the  eleventh,  twelfth,  and  thirteenth  dorsal  nerves. 
The  stimulation  of  the  nerves  entering  the  hilus  of  the  kidney  between  the 
artery  and  vein  causes  a  marked  and  sudden  renal  contraction,  hut  the  organ 
soon  regains  its  former  volume.  Constriction  follows  also  the  stimulation  of 
the  peripheral  end  of  the  cut  splanchnic  nerve.  Bradford  has  demonstrated 
renal  vaso-dilator  fibres  for  certain  nerves  by  stimulating  at  the  rate  of  one 
induction  shock  per  second.  For  example,  the  excitation  of  the  thirteenth 
dorsal  nerve  with  50  to  5  induction  shocks  per  second  gave  always  a  constric- 
tion of  the  kidney,  but  when  a  single  shock  per  second  was  employed,  the 
kidney  dilated.  If  the  cells  connected  with  the  renal  vaso-motor  fibres  are 
stimulated  directly  by  venous  blood  as  in  asphyxia,  the  animal  being  curarized, 
a  decided  constriction  of  the  kidney  results.  The  reflex  excitation  of  these 
cells  is  of  especial  importance.  The  stimulation  of  the  central  end  of  the 
sciatic  or  the  splanchnic  nerves  causes  renal  constriction.  The  same  effect  is 
easily  produced  by  stimulating  the  skin,  for  example,  by  the  application  of 
cold.  The  stimulation  of  the  sole  of  the  foot  in  a  curarized  dog  caused 
contraction  of  the  renal  vessels.  There  is  some  evidence  that  the 
splanchnic  vaso-motor  fibres  for  the  kidney  end  in  the  cells  of  the  renal 
plexus. 

Spleen. — The  stimulation  of  the  peripheral  end  of  the  splanchnic  nerves 
causes  a  sudden  and  large  diminution  in  the  volume  of  the  spleen/  It 
is,  however,  not  certain  whether  the  constriction  of  the  spleen  is  to  be 
referred  primarily  to  a  constriction  of  its  blood-vessels  or  to  the  contraction 
of  the  intrinsic  muscular  fibres  which  play  so  large  a  part  in  the  changes  of 
volume  of  this  organ.  The  doubt  is  strengthened  by  the  fact  that  section  of 
the  splanchnic  nerves  does  not  alter  the  volume  of  the  spleen  ;  dilatation 
would  be  expected  were  these  nerves  the  pathway  of  vaso-constrictor  fibres 
for  the  spleen. 

Pancreas. — Francois-Franck  and  Hallion  find  vaso-constrictor  fibres  in 
the  sympathetic  chain  between  the  sixth  and  eleventh  ribs;   they  leave  the 

spinal   cord  from   the  fifth  dorsal  to  the  second  lumbar  ramus  ( imunicans, 

pass  into  the  greater  and  lesser  splanchnic  nerves,  and  reach  the  gland  along 
the  pancreatic  artery.  A  few  dilator  fibres  were  found  in  the  sympathetic  ; 
more  in  the  the  vagus.'5 

Externa/  Generative  Organs/ — The  recent  history  of  the  vaso-motor  nerves 
of  the  external  generative  organs— namely,  those  developed  from  the  urogenital 
sinus  and  the  skin  surrounding  the   urogenital   opening — begins  with    Eck- 

1  Wertheimer :  Archives  de  Physiologic,  1894,  p.  308;  Baylisa  ami  Bradford:  Journal  of 
Physiology,  1894,  \vi.  p.  17. 

"Schaferand  Moore:  Journal  of  Physiology,  1896,  xx.  p.  1. 

3  Franck  and  Hallion:  Archives  de  Physiologie,  L896,  pp.  908,923. 

*Franck:  Archives  de  Physiologie,  1895,  p.  122;  Langle;  and  Anderson:  Journal  of  Physi- 
ology, 1895,  six.  p.  76. 


l'hs  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

hard,  who  showed  that  the  stimulation  of  certain  branches  of  the  first  and 
second,  and  occasionally  the  third,  sacral  nerves  (dog)  caused  a  dilatation  of  the 
blood-vessels  of  the  penis  and  erection  of  that  organ,  and  with  Goltz,  who 
found  an  erection  centre  in  the  lumbo-sacral  cord.  Numerous  researches  in 
recent  years,  among  which  the  reader  is  referred  especially  to  the  work  of 
Langley  and  Langley  and  Anderson,  have  shown  that  the  vaso-motor  nerves 
of  the  external  generative  organs  of  both  sexes  may  be  divided  into  a  lumbar 
and  a  sacral  group. 

The  lumbar  fibres  pass  out  of  the  cord  in  the  anterior  roots  of  the  second, 
third,  fourth,  and  fifth  lumbar  nerves,  and  run  in  the  white  rami  communi- 
cant'- to  the  sympathetic  chain,  from  which  they  reach  the  periphery  either  by 
way  of  the  pudic  nerves  or  by  the  pelvic  plexus.  The  greater  number  take 
the  former  course,  running  down  the  sympathetic  chain  to  the  sacral  ganglia, 
and  passing  from  these  ganglia  through  the  gray  rami  communicantes  to  the 
sacral  nerves.  None  of  the  fibres  thus  derived  enter  the  nervi  erigentes  of 
Eckhard.  Of  the  various  branches  of  the  pudic  nerves  (rabbit),  the  nervus 
dorsalis  causes  constriction  of  the  blood-vessels  of  the  penis  and  the  peri- 
neal nerve  contraction  of  the  blood-vessels  of  the  scrotum.  The  course  by 
way  of  the  pelvic  plexus  is  taken  by  relatively  few  fibres.  They  run  for 
the  most  part  in  the  hypogastric  nerves,  a  few  sometimes  joining  the  plexus 
from  the  lower  lumbar  or  upper  sacral  sympathetic  chain,  or  from  the 
aortic  plexus.  The  presence  of  vaso-dilator  fibres  in  the  lumbar  group  is 
disputed. 

The  sacral  group  of  nerves  leave  the  spinal  cord  in  the  sacral  nerve  roots. 
Their  stimulation  causes  dilatation  of  the  vessels  of  the  penis  and  vulva. 

Internal  Generative  Organs  (those  developed  from  the  Miillerian  or  the 
Wolffian  ducts). — Langley  and  Anderson  find  vaso-constrictor  fibres  for  the 
Fallopian  tubes,  uterus,  and  vagina  in  the  female,  and  the  vasa  deferentia  and 
seminal  vesicles  in  the  male,  in  the  second,  third,  fourth,  and  fifth  lumbar 
nerves.  The  internal  generative  organs  receive  no  afferent,  and  probably  no 
efferent,  fibres  from  the  sacral  nerves. 

The  position  of  the  sympathetic  ganglion-cells,  the  processes  of  which  carry 
to  their  peripheral  distribution  the  efferent  impulses  brought  to  them  by  the 
efferent  vaso-motor  fibres  of  the  spinal  cord,  may  be  determined  by  the  nicotin 
method  of  Langley.  About  10  milligrams  of  nicotin  injected  into  a  vein  of  a 
cat  prevent  for  a  time,  according  to  Langley,1  any  passage  of  nerve-impulses 
through  a  sympathetic  cell.  Painting  the  ganglion  with  a  brush  dipped  in 
nicotin  solution  has  a  similar  effect.  The  fibres  peripheral  to  the  cell,  on  the 
contrary,  are  not  paralyzed  by  nicotin.  Now,  after  the  injection  of  nicotin  the 
stimulation  of  the  lumbar  nerves  in  the  spinal  canal  has  no  effect  on  the  vessels 
of  the  generative  organs.  Hence  all  the  vaso-motor  fibres  of  the  lumbar 
nerves  musl  be  connected  with  nerve-cells  somewhere  on  their  course.  The 
lumbar  fibres  which  run  outward  to  the  inferior  mesenteric  ganglia  are  for  the 
most  part  connected  with  the  cells  of  these  ganglia.  A  lesser  number  is  con- 
1  Langley  and  Anderson  :  Journal  of  Physiology,  1894,  xvi.  p.  420. 


CIRCULATION.  209 

nected  with  small  ganglia  lying  as  a  rule  near  the  organs  to  which  the  nerves 
are  distributed.  The  remaining  division  of  lumbar  fibres  running  downward 
in  the  sympathetic  chain,  and  including  the  majority  of  the  nerve-fibres  to  the 
external  generative  organs  are  connected  with  nerve-cells  in  the  sacral  gan- 
glia of  the  sympathetic. 

The  sacral  group  of  nerves  enter  ganglion-cells  scattered  on  their  course, 
most  of  the  nerve-cells  for  any  one  organ  being  in  ganglia  near  that  organ. 

Bladder. — Neither  lumbar  nor  sacral  nerves  send  vaso-motor  fibres  to  the 
vessels  of  the  bladder. 

Portal  System. — It  has  already  been  said  that  vaso-constrictor  fibres  for  the 
portal  vein  were  discovered  by  Mall  in  the  splanchnic  nerve.  Constrictor  fibres 
have  been  found  by  Bayliss  and  Starling  1  in  the  nerve-roots  from  the  third  to 
the  eleventh  dorsal  inclusive.  Most  of  the  constrictor  nerves  pass  out  from 
the  fifth  to  the  ninth  dorsal. 

Back. — The  dorsal  branches  of  the  lumbar  and  intercostal  arteries,  issuing 
from  the  dorsal  muscles  to  supply  the  skin  of  the  back,2  can  be  seen  to  con- 
tract when  the  gray  ramus  of  the  corresponding  sympathetic  ganglia  are 
stimulated. 

Limbs.3 — The  vaso-motor  nerves  of  the  limbs  in  the  dog  leave  the  spinal 
cord  from  the  second  dorsal  to  the  third  lumbar  nerves.  The  area  for  the  hind 
limb,  according  to  Bayliss  and  Bradford,  is  less  extensive  than  that  for  the 
fore  limb,  the  former  receiving  constrictor  fibres  from  nine  roots,  namely  the 
third  to  the  eleventh  dorsal,  the  latter  from  six  roots,  the  eleventh  dorsal  to 
third  lumbar.  Langley  finds  that  the  sympathetic  constrictor  and  dilator 
fibres  for  the  fore  foot  are  connected  with  nerve-cells  in  the  ganglion  stella- 
tum  ;  while  those  for  the  hind  foot  are  connected  with  nerve-cells  in  the  sixth 
and  seventh  lumbar,  and  the  first,  and  possibly  the  second,  sacral  ganglia. 

Thompson  and  Bancroft  have  studied  the  nerves  to  the  superficial  veins 
of  the  hind  limb.  The  latter  finds  that  in  general  the  arrangement  of  the 
vaso-motor  nerves  corresponds  to  that  of  the  arterial  vaso-motor  nerves  and 
the  sweat  fibres.  The  fibres  to  the  superficial  veins  originate  from  the  lower 
end  (first  to  fourth  lumbar  nerves)  of  the  region  of  the  spinal  cord  supplying 
all  the  vaso-motor  nerves  for  the  hind  limbs. 

Tail.4 — Stimulation  of  any  part  of  the  sympathetic  from  about  the  third 
lumbar  ganglion  downward  almost  completely  stops  the  flow  of  blood  from 
wounds  in  the  tail.  The  vaso-motor  fibres  for  the  tail  leave  the  cord  chiefly 
in  the  third  and  fourth  lumbar  nerves.  Their  stimulation  may  cause  primary 
dilatation  followed  by  constriction. 

Muscles. — According  to  Gaskell,  the  section  of  the  nerve  belonging  to 

1  Bayliss  and  Starling:  Journal  of  Physiology,  1894,  xvii.  p.  125. 

2  Langley  :  Journal  of  Physiology,  1894,  xvii.  |>.  314. 

:1  Thompson  :  Archiv  fur  Physiohgie,  1893,  p.  104;  Wertheinier :  Archives  de  Physiologic 
1894,  p.  724;  Bancroft:  American  Journal  of  Physiology,  1898,  i.  p.  477  ;  Bayliss  and  Bradford: 
Journal  of  Physiology,  1894,  xvi.  p.  16;  Langley:  Journal  of  Physiology,  1894,  xvii.  p.  307; 
Piotrowski  :   Archiv  fur  die  ycsmnmfe  Physiologic,  1893,  lv.  p.  268. 

4  Langley  :  Journal  of  Physiology,  1894,  xvii.  p.  311. 
Vol.  I.— 14 


210  Ay    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

any  particular  muscle  or  group  of  muscles  causes  a  temporary  increase  in  the 
amount  of  blood  which  flows  from  the  muscle  vein.  The  stimulation  of  the 
peripheral  end  of  the  nerve  also  increases  the  rate  of  flow  through  the  muscle. 
The  same  increase  is  seen  on  stimulation  of  the  nerve  when  the  muscle  is  kept 
from  contracting  by  curare,  provided  the  drug  is  not  used  in  amounts  sufficient 
to  paralyze  the  vaso-dilator  nerves.  Mechanical  stimulation  by  crimping  the 
peripheral  end  of  the  nerve  gives  also  an  increase.  The  existence  of  vaso- 
dilator nerves  to  muscles  must  therefore  be  conceded.  The  presence  of  vaso-con- 
strictor  fibres  is  shown  by  the  diminution  in  outflow  from  the  left  femoral  vein 
which  followed  Gaskell's  stimulation  of  the  peripheral  end  of  the  abdominal 
sympathetic  in  a  thoroughly  curarized  dog,  but  the  supply  of  constrictor  fibres 
is  comparatively  small.  In  curarized  animals  reflex  dilatation  apparently  follows 
the  stimulation  of  the  nerves  the  excitation  of  which  would  have  caused  the 
contraction  of  the  muscles  observed,  had  not  the  occurrence  of  actual  contrac- 
tion been  prevented  by  the  curare.  The  stimulation  of  the  central  end  of 
nerves  not  capable  of  calling  forth  reflex  contractions  in  the  muscles  observed 
— for  example,  the  vagus — seems  to  cause  constriction  of  the  muscle- vessels. 


IV.  SECRETION. 


A.  General  Considerations. 

The  term  secretion  is  meant  ordinarily  to  apply  to  the  liquid  or  semi- 
liquid  products  formed  by  glandular  organs.  On  careful  consideration 
it  becomes  evideut  that  the  term  gland  itself  is  widely  applied  to  a  variety 
of  structures  differing  greatly  in  their  anatomical  organization — so  much  so, 
in  fact,  that  a  general  definition  of  the  term  covering  all  cases  becomes 
very  indefinite,  and  as  a  consequence  the  conception  of  what  is  meant  by  a 
secretion  becomes  correspondingly  extended. 

Considered  from  the  most  general  standpoint  we  might  define  a  gland 
as  a  structure  composed  of  one  or  more  gland-cells,  epithelial  in  character, 
which  forms  a  product,  the  secretion,  that  is  discharged  either  upon  a 
free  epithelial  surface  such  as  the  skin  or  mucous  membrane,  or  upon  the 
closed  epithelial  surface  of  the  blood-  and  lymph-cavities.  In  the  former  case 
— that  is,  when  the  secretion  appears  upon  a  free  epithelial  surface  communi- 
cating with  the  exterior,  the  product  forms  what  is  ordinarily  known  as  a 
secretion;  for  the  sake  of  contrast  it  might  be  called  an  external  secretion. 
In  the  latter  case  the  secretion  according  to  modern  nomenclature  is  designated 
as  an  internal  secretion.  The  best-known  organs  furnishing  internal  secretions 
are  the  liver,  the  thyroid,  and  the  pancreas.  It  remains  possible,  however, 
that  any  organ,  even  those  not  possessing  an  epithelial  structure,  such  as 
the  muscles,  may  give  off  substances  to  the  blood  comparable  to  the  internal 
secretions — a  possibility  that  indicates  how  indefinite  the  distinction  between 
the  processes  of  secretion  and  of  general  cell-metabolism  may  become  if  the 
analysis  is  carried  sufficiently  far.  If  we  consider  only  the  external  secret  ion- 
definition  and  generalization  become  much  easier,  for  in  these  cases  the  secret- 
iDg  surface  is  always  an  epithelial  structure  which,  when  it  possesses  a  certain 
organization,  is  designated  as 

a  gland.  The  type  upon  which  '♦/•rOW*  /  •  /•)  •T^T^M^7^p]^*7^R^iM  rXi. 
these  secretingsurfaecs  arecon-  ~~DQ£ 
structed  is  illustrated  in  Figure 
46.  The  type  consists  of  an 
epithelium  placed  upon  a  basement  membrane,  while  upon  the  other  side  of 
the  membrane  are  blood-capillaries  and  lymph-spaces.  The  secretion  is 
derived  ultimately  from  the  blood  and  is  discharged  upon  the  free  epithelial 
surface,  which  is  supposed  to  communicate  with  the  exterior.  The  mucous 
membrane  of  the  alimentary  canal  from  stomach  to  rectum  may  be  considered, 

■j  1 1 


46,— Plan  (if  a  Becretlne  membrane. 


212 


AN    AMERICAN    TEXT- HOOK    OF  PHYSIOLOGY. 


if  we  neglect  the  existence  of  the  villi  and  crypts,  as  representing  a  secreting 
surface  constructed  on  this  type.     If  we  suppose  such  a  membrane  to  become 


amBEEB3E33£BS 


sciw§~a 


Fig.  47.— To  illustrate  the  Bimplest  form  of  a  tubular  and  a  racemose  or  acinous  gland. 

invaginated  to  form  a  tube  or  a  sac  possessing  a  definite  lumen  (see  Fig.  47), 
we  have  then  what  may  be  designated  technically  as  a  gland. 

It  is  obvious  that  in  this  case  the  gland  may  be  a  simple  pouch,  tubular  or 
saccular  in  shape  (Fig.  48),  or  it  may  attain  a  varying  degree  of  complexity  by 
the  elongation  of  the  involuted  portion  and  the  development  of  side  branches 


lir..   is.- simple  alveolar  gland  of  the 
amphibian  skin  (after  Flemming). 


Fig.  49.— Schematic  representation  of  a  lobe  of  a 
compound  tubular  gland  (after  Flemming). 


(  Fig.  49).  The  more  complex  structures  of  this  character  are  known  sometimes 
as  compound  glands,  and  are  further  described  as  tubular,  or  racemose  (saccular), 
or  tubulo-racemose,  according  as  the  terminations  of  the  invaginations  are 
tubular,  or  saccular,  or  intermediate  in  shape.1  As  a  matter  of  fact  we  find 
the  greatest  variety  in  the  structure  of  the  glands  imbedded  in  the  cutaneous 
aud  mucous  surfaces,  a  variety  extending  from  the  simplest  form  of  crypts  or 
tubes  to  very  complicated  organs  possessing  an  anatomical  independence  and 
definite  vascular  and  nerve-supplies  as  in  the  case  of  the  salivary  glands 
or  the  kidney.  In  compound  glands  it  is  generally  assumed  that  the  terminal 
portions  of  the  tubes  alone  form  the  secretions,  and  these  are  designated  as  the 
the  acini  or  alveoli,  while  the  tubes  connecting  the  alveoli  with  the  exterior  are 
known  as  the  ducts,  and  it  is  supposed  that  their  lining  epithelium  is  devoid 
of  secretory  activity. 

The  mentions  formed  by  these  glands  are  as  varied  in  composition  as  the 
glands  are  in  structure.      If  we  neglect  the  case  of  the  so-called  reproductive 

1  Flemming  has  called  attention  to  the  fact  that  most  of  the  so-called  compound  racemose 
glands,  salivary  glands,  pancreas,  etc.,  do  not  contain  terminal  sacs  or  acini  at  the  ends  of  the 
system  of  ducts;  on  the  contrary,  the  final  secreting  portions  are  cylindrical  tubes,  and  such 
glands  are  better  designated  as  compound  tubular  glands. 


SECRETION.  213 

glands,  the  ovary  and  testis,  whose  right  to  the  designation  of  glands  is  doubt- 
ful, we  may  say  that  the  secretions  in  the  mammalian  body  are  liquid  or  semi- 
liquid  in  character  and  are  composed  of  water,  inorganic  salts,  and  various 
organic  compounds.  With  regard  to  the  last-mentioned  constituent  the  secre- 
tions differ  greatly.  In  some  cases  the  organic  substances  present  are  not  found  in 
the  blood,  and  furthermore  they  may  be  specific  to  a  particular  secretion,  so  that 
we  must  suppose  that  these  constituents  at  least  are  produced  in  the  gland 
itself.  In  other  cases  the  organic  elements  may  be  present  in  the  blood,  ami 
are  merely  eliminated  from  it  by  the  gland,  as  in  the  case  of  the  urea  found  in 
the  urine.  Johannes  Miiller  long  ago  made  this  distinction,  and  spoke  of  secre- 
tions of  the  latter  kind  as  excretions,  a  term  which  we  still  use  and  which  car- 
ries to  our  minds  also  the  implication  that  the  substances  so  named  are  waste 
products  whose  retention  would  be  injurious  to  the  economy.  Excretion  as 
above  defined  is  not  a  term,  however,  that  is  capable  of  exact  application  to 
any  secretion  as  a  whole.  Urine,  for  example,  contains  some  constituents  that 
are  probably  formed  within  the  kidney  itself,  e.  g.,  hippuric  acid  ;  while,  on 
the  other  hand,  in  most  secretions  the  water  and  inorganic  salts  are  derived 
directly  from  the  blood  or  lymph.  So,  too,  some  secretions — for  example,  the 
bile — carry  off  waste  products  that  may  be  regarded  as  mere  excretions,  and 
at  the  same  time  contain  constituents  (the  bile  salts)  that  are  of  immediate 
value  to  the  whole  organism.  Excretion  is  therefore  a  name  that  we  may 
apply  conveniently  to  the  process  of  removal  of  waste  products  from  the  body, 
or  to  particular  constituents  of  certain  secretions,  but  no  fundamental  distinc- 
tion can  be  made  between  the  method  of  their  elimination  and  that  of  the 
formation  of  secreted  products  in  general.  Owing  to  the  diversity  in  com- 
position of  the  various  external  secretions  and  the  obvious  difference  in  the 
extent  to  which  the  glandular  epithelium  participates  in  the  process  in  different 
glands,  a  general  theory  of  secretion  cannot  be  formulated.  •  The  kinds  of 
activity  seem  to  be  as  varied  as  i.s  the  metabolism  of  the  tissues  in  general. 

It  was  formerly  believed  that  the  formation  of  the  secretions  was  de- 
pendent mainly  if  not  entirely  upon  the  physical  processes  of  filtration, 
osmosis,  and  diffusion.  The  basement  membrane  with  its  lining  epithelium 
was  supposed  to  constitute  a  membrane  through  which  various  products  of  the 
blood  or  lymph  passed  by  filtration  and  diffusion,  and  the  variation  in  com- 
position of  the  secretions  was  referred  t<>  differences  in  structure  and  chemical 
properties  of  the  dialyzing  membrane.  flic  significant  point  about  this  view- 
is  that  the  epithelial  cells  were  supposed  t<»  play  a  passive  pari  in  the  process; 
the  metabolic  processes  within  the  cytoplasm  of  the  cells  were  not  believed  to 
affect  the  composition  of  the  secreted  product.  A.S  compared  with  this  view 
the  striking  peculiarity  of  modern  ideas  of  secretion  is,  perhaps,  the  import- 
ance attributed  to  the  living  structure  and  properties  of  the  epithelial  cells. 
It  is  believed  generally  now  that  the  glandular  epithelium  take-  ;i  direct  part 
in  the  production  of  some  at  least  of  the  constituents  of  the  secretions.  The 
reasons  for  this  view  will  be  brought  out  in  detail  further  on  in  describing  the 
secreting  processes  of  the  separate  glands.     Some  of  the  general   facts,  how- 


214  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

ever,  which  influenced  physiologists  in  coming  to  this  conclusion  are  as 
follows  : 

Microscopic  examination  has  demonstrated  clearly  that  in  many  cases  parts 
of  the  epithelial  cell-substance  can  be  followed  into  the  secretion.  In  the 
sebaceous  secretion  the  cells  seem  to  break  clown  completely  to  form  the  mate- 
rial of  the  secretion  ;  in  the  formation  of  mucus  by  the  goblet  cells  of  the 
mucous  membrane  of  the  stomach  and  intestines  a  portion  of  the  cytoplasm 
after  undergoing  a  mucoid  degeneration  is  extruded  bodily  from  the  cell  to 
form  the  secretion  ;  in  the  mammary  glands  a  portion  of  the  substance  of  the 
epithelial  cells  is  likewise  broken  off  and  disintegrated  in  the  act  of  secretion, 
while  in  other  glands  the  material  of  the  secretion  is  deposited  within  the  cell 
in  the  form  of  visible  granules  which  during  the  act  of  secretion  may  be 
observed  to  disappear,  apparently  by  dissolution  in  the  stream  of  water  passing 
through  the  cell.  Facts  like  these  show  that  some  at  least  of  the  products  of 
secretion  arise  from  the  substance  of  the  gland-cells,  and  may  be  considered  as 
representing  the  results  of  a  metabolism  within  the  cell-substance.  From 
this  standpoint,  therefore,  we  may  explain  the  variations  in  the  organic 
constituents  of  the  secretions  by  referring  them  to  the  different  kinds  of 
metabolism  existing  in  the  different  gland-cells.  The  existence  of  distinct 
secretory  nerves  to  many  of  the  glands  is  also  a  fact  favoring  the  view  of 
an  active  participation  of  the  gland-cells  in  the  formation  of  the  secretion. 
The  first  discovery  of  this  class  of  nerve-fibres  we  owe  to  Ludwig,  who  (in 
1851)  showed  that  stimulation  of  the  chorda  tympani  nerve  causes  a  strong 
secretion  from  the  submaxillary  gland.  Later  investigations  have  demon- 
strated the  existence  of  similar  nerve-fibres  to  many  other  glands — for 
example,  the  lachrymal  glands,  the  sweat-glands,  the  gastric  glands,  the 
pancreas.  Recent  microscopic  work  indicates  that  the  secretory  fibres  end  in 
a  fine  plexus  between  and  around  the  epithelial  cells,  and  we  may  infer  from 
this  that  the  action  of  the  nerve-iinpulses  conducted  by  these  fibres  is  exerted 
directly  upon  the  gland-cells. 

The  formation  of  the  water  and  inorganic  salts  present  in  the  various 
secretions  offers  a  problem  the  general  nature  of  which  may  be  referred  to 
appropriately  in  this  connection,  although  detailed  statements  must  be  reserved 
until  the  several  secretions  are  specially  described.  The  problem  involves, 
indeed,  not  only  the  well-recognized  secretions,  but  also  the  lymph  itself  as 
well  as  the  various  normal  and  pathological  exudations.  Formerly  the  occur- 
rence of  these  substances  was  explained  by  the  action  of  the  physical  processes 
of  filtration,  diffusion,  and  osmosis  through  membranes.  With  the  blood  under 
a  considerable  pressure  and  with  a  certain  concentration  in  salts  on  one  side 
of  the  basement  membrane,  and  on  the  other  a  Liquid  under  low  pressure  and 
differing  in  chemical  composition,  it  would  seem  inevitable  that  water  should 
filter  through  the  membrane  and  that  processes  of  osmosis  and  diffusion  should 
be  set  up,  further  changing  the  nature  of  the  secretion.  Upon  this  theory  the 
water  and  salts  in  all  secretions  were  regarded  merely  as  transudatory  prod- 
ucts, and  so  far  as  they  were  concerned  the  epithelium  was  supposed  to  act 


SECRET  I  OX.  215 

simply  as  a  passive  membrane.  This  theory  has  not  proved  entirely  acceptable 
for  various  reasons.  It  has  been  shown  that  living  membranes  offer  consider- 
able resistance  to  filtration  even  when  the  liquid  pressure  on  one  side  is  much 
greater  than  on  the  other.  Tigerstedt1  and  Santessen,  for  instance,  found 
that  a  lung  taken  from  a  frog  just  killed  gave  no  filtrate  when  its  cavity  was 
distended  by  liquid  under  a  pressure  of  18  to  20  centimeters,  provided  the 
liquid  used  was  one  that  did  not  injure  the  tissue.  If,  however,  the  lung- 
tissue  was  killed  by  heat  or  otherwise,  filtration  occurred  readily  under  the 
same  pressure.  In  some  glands,  also,  the  formation  of  the  water  and  salts, 
as  has  been  said,  is  obviously  under  the  control  of  nerve-fibres,  and  this  fact 
is  difficult  to  reconcile  with  the  idea  that  the  epithelial  cells  are  merely  pas- 
sive filters.  In  glands  like  the  kidney,  and  in  other  glands  as  well,  it  lias 
not,  as  yet,  been  shown  conclusively  that  the  amount  of  water  and  salts 
increases  in  proportion  to  the  rise  of  blood-pressure  within  the  capillaries,  as 
should  happen  if  filtration  were  the  sole  agent  at  work  ;  and  furthermore, 
certain  chemical  substances  when  injected  into  the  blood  may  increase  the 
flow  of  urine  to  an  extent  that  it  is  difficult  to  explain  by  the  use  of  the 
filtration  and  diffusion  theory  alone. 

While,  therefore,  it  cannot  be  denied  that  the  anatomical  conditions  pre- 
vailing in  the  glands  are  favorable  to  the  processes  of  filtration  and  osmosis, 
and  while  wre  are  justified  in  assuming  that  these  processes  do  actually  occur 
and  serve  to  account  in  part  for  the  appearance  of  the  water  and  inorganic 
salts,  it  seems  to  be  clear  that  in  the  present  condition  of  our  knowledge 
theories  based  on  these  factors  alone  do  not  suffice  to  explain  all  the  phe- 
nomena connected  with  the  secretion  of  water  and  salts.  Until  the  contrary  is 
definitively  proved  we  may  suppose  that  the  epithelial  cells  are  actively  con- 
cerned in  the  process.  The  way  in  which  they  act  is  not  known  ;  various 
hypotheses  have  been  advanced,  but  none  of  them  meets  all  the  facts  to 
be  explained,  and  at  present  it  is  customary  to  refer  the  matter  to  the  vital 
properties  of  the  cells — that  is,  to  the  peculiar  physical  or  chemical  properties 
connected  with  their  living  structure. 

We  may  now  pass  to  a  consideration  of  the  facts  known  witli  regard  to  the 
physiology  of  the  different  glands  considered  merely  as  secretory  organs. 
The  functional  value  of  the  secretions  will  be  found  described  in  the  sections 
on  Digestion  and   Nutrition. 

B.  Mucous  and  Albuminous  (  Serous )  Types  of  Glands  ;  Salivary 

Glands. 

Mucous  and  Albuminous  Glands. — Heidenhain  recognized  two  types 
of  glands,  the  mucous  and  the  albuminous,  basing  his  distinction  upon  the 
character  of  the  secretion  and  upon  the  histological  appearance  of  the  secreting 
cells.  The  classification  as  originally  made  was  applied  only  to  the  salivary 
glands  and  to  similar  glands  found  in  the   mucous   membranes  of  the   mouth 

1  Mittheil.  mm  physiol.  Lab.  des  Octroi,  med.-chir.  Tnsliliiis  in  Storkholm,  lSSo. 


216  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

and  oesophagus,  the  air-passages,  conjunctiva,  etc.  The  chemical  difference 
in  the  secretions  of  the  two  types  consists  in  the  fact  that  the  secretion  of  the 
albuminous  (or  serous)  glands  is  thin  and  watery,  containing  in  addition  to 
possible  enzymes  only  water,  inorganic  salts,  and  small  quantities  of  albumin  ; 
while  that  of  the  mucous  glands  is  stringy  and  viscid  owing  to  the  presence 
of  mucin.  As  examples  of  the  albuminous  glands  we  have  the  parotid  in 
man  and  the  mammalia  generally,  the  submaxillary  in  some  animals  (rabbit), 
-Mine  of  the  glands  of  the  mucous  membrane  of  the  month  and  nasal  cavities, 
and  tin.'  lachrymal  glands.  As  examples  of  the  mucous  glands,  the  submaxil- 
lary in  man  and  most  mammals,  the  sublingual,  the  orbital,  and  some  of  the 
glands  of  the  mucous  membrane  of  the  mouth-cavity,  oesophagus,  and  air- 
passages.  The  histological  appearance  of  the  secretory  cells  in  the  albuminous 
glands  is  in  typical  cases  markedly  different  from  that  of  the  cells  in  the 
mucous  glands.  In  the  albuminous  glands  the  cells  are  small  and  densely 
filled  with  granular  material,  so  that  the  cell  outlines,  in  preparations  from  the 
fresh  gland,  cannot  be  distinguished  (see  Figs.  53  and  55).  In  the  mucous 
glands,  on  the  contrary,  the  cells  are  larger  and  much  clearer  (see  Fig.  56). 
In  microscopic  preparations  of  the  fresh  gland  the  cells,  to  use  Langley's 
expression,  present  the  appearance  of  ground  glass,  and  granules  are  only 
indistinctly  seen.  Treatment  with  proper  reagents  brings  out  the  granules, 
which  are,  however,  larger  and  less  densely  packed  than  in  the  albuminous 
glands,  and  are  imbedded  in  a  clear  homogeneous  substance.  Histological 
examination  shows,  moreover,  that  in  some  glands,  e.  g.  the  submaxillary 
gland,  cells  of  both  types  occur.  Such  a  gland  is  usually  spoken  of  as  a 
mucous  gland,  since  its  secretion  contains  mucin,  but  histologically  it  is  a 
mixed  gland.  The  terms  mucous  and  albuminous  or  serous,  as  applied  to  the 
entire  gland,  are  not  in  fact  perfectly  satisfactory,  since  not  only  do  the  mucous 
gland-  usually  contain  some  secretory  cells  of  the  albuminous  type,  but  albu- 
minous glands,  such  as  the  parotid,  may  also  contain  cells  belonging  to  the 
mucous  type.  The  distinction  is  more  satisfactory  when  it  is  applied  to  the 
individual  cells,  since  the  formation  of  muciu  within  a  secreting  cell  seems  to 
present  a  definite  histological  picture,  and  we  can  recognize  microscopically  a 
mucous  cell  from  an  albuminous  cell  although  the  two  may  occur  together  in 
a  single  alveolus. 

Goblet  Cells. — The  goblet  cell-  found  in  the  epithelium  of  the  intestine 
afford  an  interesting  example  of  mucous  cells.  The  epithelium  of  the  intes- 
tine i>  a  simple  columnar  epithelium.  Scattered  among  tin  columnar  cells  are 
found  cell-  containing  mucin.  These  cells  are  originally  columnar  in  shape 
like  the  neighboring  cells,  but  their  protoplasm  undergoes  a  chemical  change 
of  such  a  character  that  mucin  is  produced,  causing  the  cell  to  become  swollen 
at  its  i'vfr  extremity,  whence  the  name  of  goblet  cell.  It  has  been  shown  that 
the  mucin  is  formed  within  the  substance  of  the  protoplasm  as  distinct  granules 
of  a  large  size,  and  that  the  amount  of  mucin  increases  gradually,  forcing  the 
nucleus  and  a  small  part  of  the  unchanged  protoplasm  toward  the  base  of  the 


SECRETION. 


21 


cell.  Eventually  the  mucin  is  extruded  bodily  into  the  lumen  of  the  intestine, 
leaving  behind  a  partially  empty  cell  with  the  nucleus  and  a  small  remnant  of 
protoplasm  (see  Fig.  50).     The  complete  life-history  of  these  cells  is  imper- 


I  i'.    "n.— Formation  of  secretion  of  mucus  in  the  goblet  cells:  A,  cell  containing  mucin;   B,  escape  of 
the  mucin  ;  C,  after  escape  of  the  mucin  (after  Paneth). 

fectly  known.  According  to  Bizzozero1  they  are  a  distinct  variety  of  cell  and 
are  not  genetically  related  to  the  ordinary  granular  epithelial  cells  by  which 
they  are  surrounded.  According  to  others,  any  of  the  columnar  epithelial  cells 
may  become  a  goblet  cell  by  the  formation  of  mucin  within  its  interior,  and 
after  the  mucin  is  extruded  the  cell  regenerates  its  protoplasm  and  becomes 
again  an  ordinary  epithelial  cell.  However  this  may  be,  the  interesting  fad 
from  a  physiological  standpoint  is  that  these  goblet  cells  are  genuine  unicellular 
mucous  glands.  Moreover,  the  deposition  of  the  mucin  in  the  form  of  definite 
granules  within  the  protoplasm  gives  histological  proof  that  this  material  is 
produced  by  a  metabolism  of  the  cell-substance  itself.  It  will  be  found  that 
the  mucin  cells  in  the  secreting  tubules  of  the  salivary  glands  exhibit  similar 
appearances.  So  far  as  is  known,  the  goblet  cells  do  not  possess  secretory 
nerves. 

Salivary  Glands. 

Anatomical  Relations. — The  salivary  glands  in  man  are  three  in  num- 
ber on  each  side — the  parotid,  the  submaxillary,  and  the  sublingual.  The 
parotid  gland  communicates  witli  the  mouth  by  a  large  duel  (Stenson's  duet) 
which  opens  upon  the  inner  surface  of  the  cheek  opposite  the  second  molar 
tooth  of  the  upper  jaw.  The  submaxillary  gland  lies  below  the  lower  jaw. 
and  its  duct  (Wharton's  duct)  opens  into  the  mouth-cavity  at  the  side  of  the 
frsenum  of  the  tongue.  The  sublingual  gland  lies  in  the  floor  of  the  mouth 
to  the  side  of  the  frsenum  and  opens  into  the  mouth-cavity  by  a  Dumber  (8  to 
20)  of  small  duets,  known  as  the  duets  of  Kivinus.  One  larger  duet  that 
runs  parallel  with  the  duct  of  Wharton  and  opens  separately  into  the  mouth- 
cavity  is  sometimes  present  in  man.  It  is  known  as  the  duel  of  Bartholin 
and  occurs  normally  in  the  dog.  In  addition  to  these  three  pairs  of  large 
glands  a  number  of  small  glands  belonging  both  to  the  albuminous  and  the 
mucous  types  arc  found  imbedded  in  the  mucous  membrane  of  the  mouth  and 


1  Archiv  fur  mikroakopische  ■  I  notomte,  1893,  Bd.  42.  S.  82. 


218 


AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 


tongue.     The  secretions  of  these  glands  contribute  to  the  formation  of  the 
saliva. 

The  course  of  the  nerve-fibres  supplying  the  large  salivary  glands  is  interest- 
ing in  view  of  the  physiological  results  of  their  stimulation.  The  description 
here  given  applies  especially  to  their  arrangement  in  the  dog.  The  parotid  gland 
receive-  its  fibres  from  two  sources — first,  cerebral  fibres  that  originate  in  the 
glosso-pharyngeal or  ninth  cranial  nerve,  pass  into  a  branch  of  this  nerve  known 
as  the  tympanic  branch  or  nerve  of  Jacobsou,  thence  to  the  small  superficial 
petrosal  nerve,  through  which  they  reach  the  otic  ganglion.  From  this  gan- 
glion they  pass  by  way  of  the  auriculotemporal  branch  of  the  inferior  max- 


Inferior  maxillary 

-    branch  of  fifth 


Glossopharyngeal 
nerve 


Petro 
ganglion 


Fig.  51.— Schematic  representation  of  the  course  of  the  cerebral  fibres  to  the  parotid  gland. 


illary  division  of  the  fifth  cranial  nerve  to  the  parotid  gland.     (A  schematic 
diagram  showing  the  course  of  these  fibres  is  giveu  in  Figure  51.)     A  second 


Facial 


Inferior  maxillary 
branch  of  fifth 


flinches 

Jto  tongue 
Branches  to  submaxiU- , 
lary  and  sublingual  ganglion 

Fig.  52.— Schematic  representation  of  the  course  of  the  chorda  tympani  nerve  to  the  submaxillary  gland. 

supply  of  nerve-fibres  is  obtained  from  the  cervical  sympathetic  nerve,  the 

fibres   reaching  the   gland  ultimately  in  the  coats  of  the  blood-vessels.      The 
submaxillary  (and  the  sublingual)  glands  receive  their  nerve-fibres  also  from 


SECRETION.  219 

two  sources.  The  cerebral  fibres  arise  from  the  brain  in  the  facial  nerve  and 
pass  out  in  the  chorda  tympani  branch  (Fig.  52).  This  latter  nerve,  after 
emerging  from  the  tympanic  cavity  through  the  Glaserian  fissure,  joins  the 
lingual  nerve.  After  running;  with  this  nerve  for  a  short  distance,  the  secre- 
tory  (and  vaso-dilator)  nerve-fibres  destined  for  the  submaxillary  and  sublin- 
gual glands  branch  off  and  pass  to  the  glands,  following  the  course  of  the 
ducts.  Where  the  chorda  tympani  fibres  leave  the  lingual  there  is  a  small 
ganglion  which  has  received  the  name  of  submaxillary  ganglion.  The  nerve- 
fibres  to  the  glands  pass  close  to  this  ganglion,  but  Langley  has  shown  that 
only  those  destined  for  the  sublingual  gland  really  connect  with  the  nerve- 
cells  of  the  ganglion,  and  he  suggests  therefore  that  it  should  be  called  the 
sublingual  instead  of  the  submaxillary  ganglion.  The  nerve-fibres  for  the 
submaxillary  gland  make  connections  with  nerve-cells  mainly  within  the 
hilus  of  the  gland  itself.  The  submaxillary  and  sublingual  glands  receive 
also  sympathetic  nerve-fibres,  which  after  leaving  the  superior  cervical  gan- 
glion pass  to  the  glands  in  the  coats  of  the  blood-vessels. 

Histological  Structure. — The  salivary  glands  belong  to  the  type  of  com- 
pound tubular  glands,  as  Flemming  has  pointed  out.  That  is,  the  secreting 
portions  are  tubular  in  shape,  although  in  cross  sections  these  tubes  may 
present  various  outlines  according  as  the  plane  of  the  section  passes  through 
them.  The  parotid  is  described  usually  as  a  typical  serous  or  albuminous 
gland.  Its  secreting  epithelium  is  composed  of  cells  which  in  the  fresh  con- 
dition as  well  as  in  preserved  specimens  contain  numerous  fine  granules  (see 
Figs.  53  and  55,  A).  Heidenhain  states  that  in  exceptional  cases  (in  the 
dog)  some  of  the  secreting  cells  may  belong  to  the  mucous  type.  The  base- 
ment membrane  is  composed  of  flattened  branched  connective-tissue  cells,  the 
interstices  between  which  are  filled  by  a  thin  membrane.  The  submaxillary 
gland  differs  in  histology  in  different  animals.  In  some,  as  the  dog  or  cat, 
all  the  secretory  tubes  are  composed  chiefly  or  exclusively  of  epithelial  cells 
of  the  mucous  type  (Fig.  56).  In  man  the  gland  is  of  a  mixed  type,  the 
secretory  tubes  containing  both  mucous  and  albuminous  cells.  The  sublingual 
gland  in  man  also  contains  both  varieties  of  cells,  although  the  mucous  cells 
predominate.  It  follows  from  these  histological  characteristics  that  the  secre- 
tion from  the  submaxillary  and  sublingual  glands  is  thick  and  mucilaginous  as 
compared  with  that  from  the  parotid. 

In  the  mucous  glands  another  variety  of  cells,  the  so-called  demilunes  or 
crescent  cells,  is  frequently  met  with  ;  and  the  physiological  significance  of 
these  cells  has  been  the  subject  of  much  discussion.  The  demilunes  are  cres- 
cent-shaped granular  cells  lying  between  the  mucous  cells  and  the  basement 
membrane,  and  not  in  contact,  therefore,  with  the  central  lumen  of  the  tube 
(see  Fig.  56).  According  to  Heidenhain  these  demilunes  are  for  the  purpose 
of  replacing  the  mucous  cells.  In  consequence  of  long-continued  activity  the 
mucous  cells  may  disintegrate  and  disappear,  and  the  demilunes  then  develop 
into  new  mucous  cells.  The  most  probable  view  at  present  is  that  the  demi- 
lunes represent  distinct  secretory  cells  of  the  albuminous  type. 


220  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

The  secreting  tubules  of  the  salivary  glands  possess  distinct  lumens 
round  which  the  cells  are  arranged.  In  addition  a  number  of  recent  observers, 
making  use  of*  the  Grolgi  method  of  staining,  have  apparently  demonstrated 
thai  in  the  albuminous  glands  the  Lumen  is  continued  as  fine  capillary  spaces 
running  between  the  secreting  cells.1  The  statement  is  also  made  that  1'rom 
these  secretion  capillaries  small  side-branches  are  given  off  that  penetrate 
into  the  substance  of  the  cell,  making  an  intracellular  origin  of  the  system  of 
duets  ;  this  point,  however,  needs  confirmation.  In  the  mucous  glands  similar 
secretion  capillaries  an'  found  only  in  connection  with  the  demilunes.  This 
latter  fact  supports  the  view  that  the  demilunes  are  not  simply  inactive  forms 
of  mucous  cells,  hut  cells  with  a  specific  functional  activity.  It  is  an  nu- 
ll. ml)ted  fact  that  the  salivary  glands  possess  definite  secretory  nerves  which 
when  stimulated  start  the  formation  of  secretion.  This  fact  indicates  that 
there  must  be  a  direct  contact  of  some  kind  between  the  gland-cells  and  the 
terminations  of  the  secretory  fibres.  The  nature  of  this  connection  has  been 
the  subject  of  numerous  investigations,  the  results  of  which  were  for  a  long  time 
negative  or  untrustworthy.  More  recently,  however,  the  application  of  the 
useful  Gol«;i  method  has  led  to  satisfactorv  results.  The  ending  of  the  nerve- 
fibres  in  the  submaxillary  and  sublingual  glands  has  been  described  by  a  num- 
ber of  observers.2  The  accounts  differ  somewhat  as  to  details  of  the  finer 
anatomv,  but  it  seems  to  be  clearly  established  that  the  secretory  fibres  from 
the  chorda  tympani  end  first  round  the  intrinsic  nerve-ganglion  cells  of  the 
glands,  and  from  these  latter  cells  axis-cylinders  are  distributed  to  the 
secreting  cells,  passing  to  these  cells  along  the  ducts.  The  nerve-fibres  termi- 
nate in  a  plexus  upon  the  membrana  propria  of  the  alveoli,  and  from  this 
plexus  fine  fibrils  pass  inward  to  end  on  and  between  the  secreting  cells. 
It  would  seem  from  these  observations  that  the  nerve-fibrils  do  not  penetrate 
or  fuse  with  the  gland-cells,  as  was  formerly  supposed,  but  form  a  terminal 
network  in  contact  with  the  cells,  following  thus  the  general  schema  for  the 
connection  between  nerve-fibres  and  peripheral  tissues. 

Composition  of  the  Secretion. — The  saliva  as  it  is  found  in  the;  mouth 
is  a  mixed  secretion  from  the  large  salivary  elands  and  the  numerous 
smaller  glands  scattered  over  the  mucous  membrane  of  the  mouth.  It  is  a 
colorless  or  opalescent,  turbid,  and  mucilaginous  liquid  of  weakly  alkaline  re- 
action and  a  specific  gravity  of  about  1003.  It  may  contain  numerous  flat 
c,ll~  derived  from  the  epithelium  of  the  mouth,  and  the  peculiar  spherical  cell- 
known  as  salivary  corpuscles,  which  seem  to  be  altered  leucocytes.  The  im- 
portant constituents  of  the  secretion  are  mucin,  a  diastatic  enzyme  known  as 
ptvalin,  traces  of  albumin  and  of  potassium  sulphocyanide,  and  inorganic  salts 
such  a-  potassium  and  -odium  chloride,  potassium  sulphate,  sodium  carbonate, 
and  calcium  carbonate  and  phosphate.  The  average  proportions  of  these  con- 
stituent- is  given  in  the  following  analysis  by  Hammerbacher : 

1  Laserstein:    Pfliiger'a  Archiv  fur  die  gesammte  Physiologie,  1893,  Bd.  ■">•">,  S.  417. 
•    Huber :   Journal  of  Efi>rrhncnt<il  Medicim,  ls'.it',,  vol.  i.  ]>.  "J*l. 


SECRETION.  221 

Water, 99-1.203 

Solids : 

Mucin  and  epithelial  cells, 2.202 

Ptyalin  and  albumin, 1.390 

Inorganic  salts, 2.205 

5.797 

1.000.000 
(Potassium  sulphocyanide,  0.041.) 

Of  the  organic  constituents  of  the  saliva  the  proteid  exists  in  small  and  varia- 
ble quantities,  and  its  exact  nature  is  not  determined.  The  mucin  gives  to  the 
saliva  its  ropy,  mucilaginous  character.  This  substance  belongs  to  the  group 
of  combined  proteids,  glyco-proteids  (see  section  on  Chemistry),  consisting  of  a 
proteid  combined  with  a  carbohydrate  group.  The  physiological  value  of  this 
constituent  seems  to  lie  in  its  physical  properties,  as  described  in  the  section  on 
Digestion.  The  most  interesting  constituent  of  the  mixed  saliva  is  the  pty- 
alin. This  body  belongs  to  the  group  of  enzymes  or  unorganized  ferments, 
whose  general  and  specific  properties  are  described  in  the  section  on  Digestion. 
It  suffices  here  to  say  only  that  ptyalin  belongs  to  the  diastatic  group  of  enzymes, 
whose  specific  action  consists  in  a  conversion  of  the  starches  into  sugar  by  a  proc- 
ess of  hydrolysis.  In  some  animals  (dog)  ptyalin  seems  to  be  normally  absent 
from  the  fresh  saliva.  An  interesting  fact  with  reference  to  the  saliva  is  the 
large  quantity  of  gases,  particularly  0O2,  which  may  be  obtained  from  it  when 
freshly  secreted.  In  an  analysis  by  Pfliiger  of  the  saliva  from  the  submaxil- 
lary gland  the  following  figures  were  obtained:  C02,  65  per  cent.,  of  which 
42.5  per  cent,  was  in  the  form  of  carbonates;  N,  0.8  per  cent.  ;  O,  0.6  per 
cent.  For  the  parotid  secretion  Kiilz  reports:  CG2,  66.7  per  cent.,  (if  which 
62  per  cent,  was  in  combination  as  carbonate;  N,  3.8  per  cent.  ;  O,  1.46  per 
cent. 

The  secretions  of  the  parotid  and  submaxillary  glands  can  be  obtained  easily 
by  inserting  a  cannula  into  the  openings  of  the  duets  in  the  mouth.  The  secre- 
tion of  the  sublingual  can  only  be  obtained  in  sufficient  quantities  for  analysis 
from  the  lower  animals.  Examination  of  the  separate  secretions  shows  that  the 
main  difference  lies  in  the  fact  that  the  parotid  saliva  contains  no  mucin,  while 
that  of  the  submaxillary  and  especially  of  the  sublingual  gland  is  rich  in 
mucin.  The  parotid  saliva  of  man  seems  to  be  particularly  rich  in  ptyalin  as 
compared  with  that  of  the  submaxillary,  while  the  secretion  of  the  latter  and 
that  of  the  sublingual  gland  give  a  stronger  alkaline  reaction  than  the  parotid 
saliva. 

The  Secretory  Nerves. — The  existence  of  secretory  nerves  was  discovered 
by  Ludwig  in  1851.  He  found  that  stimulation  of  the  chorda  tympani  nerve 
caused  a  How  of  saliva  from  the  submaxillary  gland.  He  established  also 
several  important  facts  with  regard  to  the  pressure  and  composition  of  the 
secretion  which  will  be  referred  to  presently.  It  was  afterward  shown  that, 
the  salivary  glands  receive  a  double  nerve-supply,  in  pari  by  way  of  the 
cervical  sympathetic  and  in  part  through  cerebral  nerves,  as  briefly  described 
on  p.  218.     It  was  discovered  also  that    not  only  arc  secretory  fibres  carried 


222  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

to  the  glands  by  these  paths,  but  that  the  vaso-motor  fibres  are  contained  in 
tli''  same  nerves,  and  the  arrangement  of  these  latter  fibres  is  such  that  the 
cerebral  nerves  contain  vaso-dilator  fibres  that  cause  a  dilatation  of  the  small 
arteries  in  the  glands  and  an  accelerated  blood-flow,  while  the  sympathetic 
carries  vaso-constrictor  fibres  whose  stimulation  causes  a  constriction  of  the 
small  arteries  and  a  diminished  blood-flow.  The  effect  upon  the  secretion  of 
stimulating  these  two  sets  of  fibres  is  found  to  vary  somewhat  in  different 
animals.  For  purposes  of  description  we  may  confine  ourselves  to  the  effects 
observed  on  dogs,  since  much  of  our  fundamental  knowledge  upon  the  subject 
is  derived  from  Heidenhain's1  experiments  upon  this  animal.  If  the  chorda 
tympani  nerve  is  stimulated  by  weak  induction  shocks,  the  gland  begins  to 
secrete  promptly,  and  the  secretion,  by  proper  regulation  of  the  stimuli,  may 
be  kept  up  for  hours.  The  secretion  thus  obtained  is  thin  and  watery,  flows 
freely,  is  abundant  in  amount,  and  contains  not  more  than  1  or  2  per  cent,  of 
total  solids.  At  the  same  time  there  is  an  increased  flow  of  blood  through 
tin  gland.  The  whole  gland  takes  on  a  redder  hue,  the  veins  are  distended, 
and  if  cut  the  blood  that  flows  from  them  is  of  a  redder  color  than  in  the 
resting  gland,  and  may  show  a  distinct  pulse — all  of  which  points  to  a  dilata- 
tion of  the  small  arteries.  If  now  the  sympathetic  fibres  are  stimulated,  quite 
different  results  are  obtained.  The  secretion  is  relatively  small  in  amount, 
Hows  slowly,  is  thick  and  turbid,  and  may  contain  as  much  as  6  per  cent,  of 
total  solids.  At  the  same  time  the  gland  becomes  pale,  and  if  the  veins  be 
cut  the  flow  from  them  is  slower  than  in  the  resting  gland,  thus  indicating 
that  a  vaso-constrietion  has  occurred. 

The  increased  vascular  supply  to  the  gland  accompanying  the  abundant 
flow  of  "chorda  saliva"  and  the  diminished  flow  of  blood  during  the  scanty 
secretion  of  "sympathetic  saliva"  suggest  naturally  the  idea  that  the  whole 
process  of  secretion  may  be  at  bottom  a  vaso-motor  phenomenon,  the  amount 
of  secretion  depending  only  on  the  quantity  and  pressure  of  the  blood  flowing 
through  the  gland.  It  has  been  shown  conclusively  that  this  idea  is  erro- 
neous and  that  definite  secretory  fibres  exist.  The  following  facts  may  be 
quoted  in  support  of  this  statement:  (1)  Ludwig  showed  that  if  a  mercury 
manometer  is  connected  with  the  duct  of  the  submaxillary  gland  and  the 
chorda  is  then  stimulated  for  a  certain  time,  the  pressure  in  the  duct  may 
become  greater  than  the  blood-pressure  in  the  gland.  This  fact  shows  that 
the  secretiou  is  not  derived  entirely  by  processes  of  filtration  from  the  blood. 
(2)  If  the  blood-How  be  shu  toll'  completely  from  the  gland,  stimulation  of 
the  chorda  will  still  give  a  secretion  for  a  short  time.  (3)  If  atropin  is 
injected  into  the  gland,  stimulation  of  the  chorda  will  cause  vascular  dilata- 
tion but  no  secretion.  This  may  be  explained  by  supposing  that  the  atropin 
paralyzes  the  secretory  but  not  the  dilator  fibres.  (4)  Hydrochlorate  of  qui- 
nine injected  into  the  gland  gives  vascular  dilatation   but  no  secretiou.     In 

1  Pjlii'irr's  Arrhir  fiir  die  r/extniDiilr  I'lii/sin/in/ir,  1878,  Bd.  xvii.  S.  1  ;  also  in  Hermann's  Hand- 
buck  der  Physiologic,  1SSI],  Bel.  v.  Tli.  1. 


SECRETIOX.  223 

this  case  the  secretory  fibres  are  still  irritable,  since  stimulation  of  the  chorda 
gives  the  usual  secretion. 

A  still  more  marked  difference  between  the  effect  of  stimulation  of  the 
cerebral  and  the  sympathetic  fibres  may  be  observed  in  the  case  of  the  parotid 
gland  in  the  dog.  Stimulation  of  the  cerebral  fibres  alone  in  any  part  of 
their  course  (see  Fig.  51)  gives  an  abundant  thin  and  watery  saliva,  poor  in 
solid  constituents.  Stimulation  of  the  sympathetic  fibres  alone  (provided  the 
cerebral  fibres  have  not  been  stimulated  shortly  before  (Laugley)  and  the  tym- 
panic nerve  has  been  cut  to  prevent  a  reflex  effect)  gives  usually  no  perceptible 
secretion  at  all.  But  in  this  last  stimulation  a  marked  effect  is  produced  upon 
the  gland,  in  spite  of  the  absence  of  a  visible  secretion  ;  this  is  shown  by  the 
fact  that  subsequent  or  simultaneous  stimulation  of  the  cerebral  fibres  gives  a 
secretion  very  unlike  that  given  by  the  cerebral  fibres  alone,  in  that  it  is  very 
rich  indeed  in  organic  constituents.  The  amount  of  organic  matter  in  the 
secretion  may  be  tenfold  that  of  the  saliva  obtained  by  stimulation  of  the 
cerebral  fibres  alone. 

Another  important  and  suggestive  set  of  facts  with  regard  to  the  action  of 
the  secretorv  nerves  is  obtained  from  a  study  of  the  differences  in  composition 
of  the  secretion  following  upon  variations  in  the  strength  of  stimulation  of  the 
nerves. 

Relation  of  the  Composition  of  the  Secretion  to  the  Strength  of  Stimula- 
tion.— If  the  stimulus  to  the  chorda  is  gradually  increased  in  strength, 
care  being  taken  not  to  fatigue  the  gland,  the  chemical  composition  of  the 
secretion  is  found  to  change  with  regard  to  the  relative  amounts  of  the 
water,  the  salts,  and  the  organic  material.  The  water  and  the  salts  increase 
in  amount  with  the  increased  strength  of  stimulus  up  to  a  certain  maximal 
limit,  which  for  the  salts  is  about  0.77  per  cent.  It  is  important  to  observe 
that  this  effect  may  be  obtained  from  a  perfectly  fresh  gland  as  well  as 
from  a  gland  which  had  previously  been  secreting  actively.  With  regard 
to  the  organic  constituents  the  precise  result  obtained  depends  on  the  con- 
dition of  the  gland,  li'  previous  to  the  stimulation  the  gland  was  in  a 
resting  condition  and  unf'atigued,  then  increased  strength  of  stimulation  i- 
followed  at  first  by  a  rise  in  the  percentage  of  organic  constituents,  and  this 
rise  in  the  beginning  is  more  marked  than  in  the  case  of  the  salts.  lint 
with  continued  stimulation  the  increase  in  organic  material  soon  ceases,  and 
finally  the  amount  begins  actually  to  diminish,  and  may  fall  to  a  low  point 
in  spite  of  the  stronger  stimulation.  On  the  other  hand,  if  the  gland  in  the 
beginning  of  the  experiment  had  been  previously  worked  to  a  considerable 
extent,  then  an  increase  in  the  stimulating  current,  while  it  increases  the 
amount  of  water  and  salts,  may  have  either  no  effect  at  all  upon  the  organic 
constituents  or  cause  only  a  temporary  increase,  quickly  followed  by  a  fall. 
Similar  results  may  be  obtained  from  stimulation  of  the  cerebral  nerves  of 
the  parotid  gland.  The  above  facts  led  Heidenhain  to  believe  that  the  con- 
ditions determining  the  secretion  of  the  organic  material  are  different   from 


224  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

those  controlling  the  water  and  salts,  and  he  gave  a  rational  explanation  of 
the  differences  observed,  in  his  theory  of  trophic  and  secretory  fibres. 

Theory  of  Trophic  and  Secretory  Nerve-fibres. — This  theory  supposes 
that  two  physiological  varieties  of  nerve-fibres  are  distributed  to  the  salivary 
glands.  One  of  these  varieties  controls  the  secretion  of  the  water  and  inor- 
ganic  -alts  and  it>  fibres  may  be  called  secretory  fibres  proper,  while  the  other, 
to  which  the  name  trophic  is  given,  causes  the  formation  of  the  organic  con- 
stituents of  the  secretion,  probably  by  a  direct  influence  on  the  metabolism  in 
the  cell.  Were  the  trophic  fibres  to  act  alone,  the  organic  products  would  be 
formed  within  the  cell  but  there  would  be  no  visible  secretion,  and  this  is 
the  hypothesis  which  Ileidenhain  uses  to  explain  the  results  of  the  experi- 
ment described  above  upon  stimulation  of  the  sympathetic  fibres  to  the  parotid 
of  the  dog.  In  this  animal,  apparently,  the  sympathetic  branches  to  the  parotid 
contain  exclusively  or  almost  exclusively  trophic  fibres,  while  in  the  cerebral 
branches  both  trophic  and  secretory  fibres  proper  are  present.  The  results  of 
stimulation  of  the  cerebral  and  sympathetic  branches  to  the  submaxillary  gland 
of  the  same  animal  may  be  explained  in  terms  of  this  theory  by  supposing  that 
in  the  latter  nerve  trophic  fibres  preponderate,  and  in  the  former  the  secretory 
fibres  proper. 

1 1  is  obvious  that  this  anatomical  separation  of  the  two  sets  of  fibres  along  the 
cerebral  and  sympathetic  paths  may  be  open  to  individual  variations,  and  that 
dogs  may  be  found  in  which  the  sympathetic  branches  to  the  parotid  glands 
contain  secretory  fibres  proper,  and  therefore  give  some  flow  of  secretion  on 
stimulation.  These  variations  might  also  be  expected  to  be  more  marked  when 
animals  of  different  groups  are  compared.  Thus  Langley1  finds  that  in  cats  the 
sympathetic  saliva  from  the  submaxillary  gland  is  less  viscid  than  the  chorda 
saliva,  just  the  reverse  of  what  occurs  in  the  dog.  To  apply  Heidenhain's 
theory  to  this  case  it  is  necessary  to  assume  that  in  the  cat  the  trophic  fibres 
run  chiefly  in  the  chorda.  An  interesting  fact  with  reference  to  the  secretion 
of  the  parotid  in  dogs  has  been  noted  by  Langley  and  is  of  special  interest, 
since,  although  it  may  be  reconciled  with  the  theory  of  trophic  and  secretory 
fibres,  it  is  at  the  same  time  suggestive  of  an  incompleteness  in  this  theory. 
As  has  been  said,  stimulation  of  the  sympathetic  in  the  dog  causes  usually  no 
secretion  from  the  parotid.  Langley2  finds,  however,  that  if  the  tympanic 
nerve  is  stimulated  just  previously,  stimulation  of  the  sympathetic  causes 
an  abundant  but  brief  flow  from  the  parotid.  One  may  explain  this  in  terms 
of  the  theory  by  assuming  that  the  sympathetic  does  contain  a  few  se- 
cretory fibre-  proper,  but  that  ordinarily  their  action  is  too  feeble  to  start 
the  flow  of  water.  Previous  stimulation  of  the  tympanic  nerve,  however, 
haves  the  gland-cells  in  a  more  irritable  condition,  so  that  the  few  secretory 
fibres  proper  in  the  sympathetic  branches  are  now  effective  in  producing  a 
flow  of  water. 

1  Journal  of  Physiology,  1878,  vol.  i.  p.  96. 
'Ibid.,  1889,  vol.  x.  p.  291. 


SECRETION.  225 

Theories  of  the  Action  of  Trophic  and  Secretory  Fibres. — The  way 
in  which  the  trophic  fibres  act  has  been  briefly  indicated.  They  may  be  sup- 
posed to  set  up  metabolic  changes  in  the  protoplasm  of  the  cells,  leading  to  the 
formation  of  certain  definite  products,  such  as  mucin  or  ptyalin.  That  sucli 
changes  do  occur  is  abundantly  shown  by  microscopic  examination  of  the  rest- 
ing and  the  active  gland,  the  details  of  which  will  be  given  presently.  In 
general  these  changes  may  be  supposed  to  be  katabolic  in  nature;  that  is,  to 
consist  in  a  disassociation  or  breaking  down  of  the  complex  living  material 
with  the  formation  of  the  simpler  and  more  stable  organic  constituents  of  the 
secretion.  There  is  evidence  to  show  that  these  gland-cells  during  activity 
form  fresh  material  from  the  nourishment  supplied  by  the  blood;  that 
is,  that  anabolic  or  building-up  processes  occur  along  with  the  katabolic 
changes.  The  latter  are  the  more  obvious  and  are  the  changes  which  are 
usually  associated  with  the  action  of  the  trophic  nerve-fibres.  It  is  possible, 
also,  that  the  anabolic  or  growth  changes  may  be  under  the  control  of  separate 
fibres  for  which  the  name  anabolic  fibres  would  be  appropriate.  Satisfactory 
proof  of  the  existence  of  a  separate  set  of  anabolic  fibres  has  not  yet  been 
furnished. 

The  method  of  action  of  the  secretory  fibres  proper  is  difficult  to  under- 
stand. At  present  the  theories  suggested  are  very  speculative,  and  a  detailed 
account  of  them  is  scarcely  appropriate  in  this  place.  Heidenhain's  own  view 
may  be  mentioned,  but  it  should  be  borne  in  mind  that  it  is  only  an  hy- 
pothesis, the  truth  of  which  is  far  from  being  demonstrated.  The  theory  starts 
from  the  fact  that  no  more  water  leaves  the  blood-capillaries  than  afterward 
appears  in  the  secretion ;  that  is,  no  matter  how  long  the  secretion  continues, 
the  gland  does  not  become  ©edematous  nor  does  the  velocity  of  the  lymph- 
stream  in  the  lymphatics  of  the  gland  increase.  This  being  the  case,  we  must 
suppose  that  the  stream  of  water  is  regulated  by  the  secretion,  that  is,  by  the 
activity  of  the  gland-cells.  If  we  suppose  that  some  constituent  of  these  cells 
has  an  attraction  for  water,  or,  to  use  the  modern  expression,  exerts  a  high 
osmotic  pressure,  then,  while  the  gland  is  in  the  resting  state,  water  will 
diffuse  from  the  basement  membrane;  this  in  turn  supplies  its  loss  from  the 
surrounding  lymph,  and  the  lymph  obtains  the  same  amount  of  water  from 
the  blood.  As  the  amount  of  water  in  the  cell  increases  a  point  is  reached 
at  which  an  equilibrium  is  established,  and  the  osmotic  stream  from  blood 
to  cells  comes  to  a  standstill.  The  water  in  the  cells  does  not  escape  into  the 
lumen  of  the  tubule  or  of  the  secretion  capillaries,  because  the  periphery  of 
the  cell  is  modified  to  form  a  layer  offering  considerable  resistance  to  filtra- 
tion. The  action  of  the  secretory  fibres  proper  consists  in  so  altering  the 
structure  of  this  limiting  layer  of  the  cells  that  it  oilers  less  resistance  to  filtra- 
tion ;  consequently  the  water  under  tension  in  the  cells  escapes  into  the  lumen, 
and  the  osmotic  pressure  of  its  substance  again  starts  up  a  stream  of  water 
from  capillaries  to  cells,  which  continues  as  long  as  the  Qerve-stim illation  is 
effective. 

Vol.  I.— 15 


226  AN   AMERICAN    TEXT- BOOK    OF   PHYSIOLOGY. 

Recent  work  by  Ranvier,  Drasch,  Biedermann,  and  others  has  called  atten- 
tion to  an  interesting  phenomenon  occurring  in  gland-cells  during  secretion 
which  when  better  known  will  possibly  throw  light  upon  the  formation  of  the 
water  stream  under  the  influence  of  nerve-stimulation.  Ranvier1  describes 
in  both  serous  and  mucous  cells  the  formation  of  vacuoles  within  the  proto- 
plasmic substance.  These  vacuoles  are  particularly  abundant  after  nerve- 
stimulation.  They  seem  to  contain  water,  and  if  they  behave  as  they  do  in 
the  protozoa — and  this  is  indicated  by  the  observations  of  Drasch2  upon  the 
glands  in  the  nictitating  membrane  in  the  frog — they  would  seem  to  form  a 
mechanism  sufficient  to  force  water  from  the  cells  into  the  lumen. 

Histological  Changes  during  Activity. — The  cells  of  both  the  albu- 
minous and  mucous  glands  undergo  distinct  histological  changes  in  conse- 
quence of  prolonged  activity,  and  these  changes  may  be  recognized  both  in 
preparations  from  the  fresh  gland  and  in  preserved  specimens.  In  the  parotid 
gland  Heidenhain  studied  the  changes  in  stained  sections  after  hardening  in 
alcohol.     In  the  resting  gland  (Fig.  53)  the  cells  are  compactly  filled  with 


Fig.  53.— Parotid  of  the  rabbit,  in  the  resting  condition  (after  Heidenhain). 

granules  that  stain  readily  and  are  imbedded  in  a  clear  ground  substance 
thai  does  not  stain.  The  nucleus  is  small  and  more  or  less  irregular  in  out- 
line. After  stimulation  of  the  tympanic  nerve  the  cells  show  but  little  altera- 
tion, but  stimulation  of  the  sympathetic  produces  a  marked  change  (Fig.  54). 
The  cells  become  Bmaller,  the  nuclei  more  rounded,  and  the  granules  more 
closely  packed.  This  last  appearance  seems,  however,  to  be  due  to  the  hard- 
ening reagents  used.  A  truer  picture  of  what  occurs  may  be  obtained  from  a 
Mu.lv  of  sections  of  the  fresh  -land.     Langley,3  who  first  used  this  method, 

1  Comptes  rendus,  cxviii.,  1,  p.  K'>s.        2  Archivfiir  AnatomU  wnd  1'lojsiologie,  1889,  S.  96. 
8  Journal  of  Physiology,  1879,  vol.  ii.  p.  260. 


SECRETION. 


227 


describes  his  results  as  follows :    When  the  animal  is  in  a  fasting  condition  the 
cells  have  a  granular  appearance  throughout  their  substance,  the  outlines  of 


Wt^m^. 


^i.ftSs^jj 


5k; 


Fig.  54.— Parotid  of  the  rabbit,  after  stimulation  of  the  sympathetic  (after  Heidenhain). 

the  different  cells  being  faintly  marked  by  light  lines  (Fig.  55,  A).  When 
the  gland  is  made  to  secrete  by  giving  the  animal  food,  by  injecting  pilocarpin, 
or  by  stimulating  the  sympathetic  nerves,  the  granules  begin  to  disappear  from 


^Sftfe-* 


C  D 

Fig.  55.— Parotid  gland  of  the  rabbit  in  a  fresh  state,  showing  portions  of  the  secreting  tubules  :  .1.  in 
a  resting  condition  ;  /;,  after  secretion  caused  by  pilocarpin  ;  ( '.  after  stronger  Becretion,  pilocarpin  and 
stimulation  of  sympathetic ;  D,  after  Long-continued  stimulation  of  Bympathel  Ic  (after  Langley). 

the  outer  borders  of  the  cells  (Fig.  -r)'r),  />),  so  that  each  cell  now  shows  an  outer 
clear  border  and  an  inner  granular  one.  If  the  stimulation  is  continued  the 
granules  become  fewer  in  number  and  are  collected  near  the  Lumen  and  the  mar- 


228 


AN   AMERICAN    TEXT- BOOK    OF    PHYSIOLOGY. 


gins  of  the  cells,  the  clear  zone  increases  in  extent  and  the  cells  become  smaller 
(Fig.  55,  C,  D).  Evidently  the  granular  material  is  used  up  in  some  way  to 
make  the  organic  material  of  the  secretion.  Since  the  ptyalin  is  a  conspicuous 
organic  constituent  of  the  secretion,  it  is  assumed  that  the  granules  in  the  rest- 
ing gland  contain  the  ptyalin,  or  rather  a  preliminary  material  from  which  the 
ptyalin  is  constructed  during  the  act  of  secretion.  On  this  latter  assumption 
the  granules  are  frequently  spoken  of  as  zymogen  granules.  During  the  act 
of  secretion  two  distinct  processes  seem  to  be  going  on  in  the  cell,  leaving  out 
of  consideration  for  the  moment  the  formation  of  the  water  and  the  salts.  In 
the  first  place  the  zymogen  granules  undergo  a  change  such  that  they  are  forced 
or  dissolved  out  of  the  cell,  and,  second,  a  constructive  metabolism  or  an- 
abolism  is  set  up,  leading  to  the  formation  of  new  protoplasmic  material  from 
the  substances  contained  in  the  blood  and  lymph.  The  new  material  thus 
formed  is  the  clear,  non-granular  substance,  which  appears  first  toward  the 
basal  sides  of  the  cells.  We  may  suppose  that  the  clear  substance  during  the 
resting  periods  undergoes  metabolic  changes,  whether  of  a  katabolic  or  anabolic 
character  cannot  be  safely  asserted,  leading  to  the  formation  of  new  granules, 
and  the  cells  are  again  ready  to  form  a  secretion  of  normal  composition.  It 
should  be  borne  in  mind  that  in  these  experiments  the  glands  were  stimulated 
beyond  normal  limits.  Under  ordinary  conditions  the  cells  are  probably  never 
depleted  of  their  granular  material  to  the  extent  represented  in  the  figures. 

In  the  cells  of  the  mucous  glands  changes  equally  marked  may  be  observed 
after  prolonged  activity.  In  stained  sections  of  the  resting  gland,  according 
to  Heidenhain,  the  cells  are  large  and  clear  (Fig.  56),  with  flattened  nuclei 


Fk;.  56.— Mucous  gland :  submaxillary  of  dog ;  rest-        Fio.  57.— Mucous  jdaud:  submaxillary  of  dog 
ing  stage.  after  eight  hours'  stimulation  of  the  chorda  tym- 

pani. 

placed  well  toward  the  base  of  the  cell.  When  the  gland  is  made  to  secrete 
the  nuclei  become  more  spherical  and  lie  more  toward  the  middle  of  the  cell, 
and  the  cells  themselves  become  distinctly  smaller.  After  prolonged  secretion 
the  changes  become  more  marked  (Fig.  57)  and,  according  to  Heidenhain,  some 
of  the  mucous  cells  may  break  down  completely.  According  to  most  of  the 
later  observers,  however,  the  mucous  cells  do  not  actually  disintegrate,  but 


SECRETIOX.  229 

form  again  new  material  during  the  period  of  rest  as  was  described  for  the 
goblet  cells  of  the  intestine.  In  the  mucous  as  in  the  albuminous  cells  ob- 
servations upon  pieces  of  the  fresh  gland  seem  to  give  more  reliable  results 
than  those  upon  preserved  specimens.  Langley  x  has  shown  that  in  the  fresh 
mucous  cells  of  the  submaxillary  gland  numerous  large  granules  may  be 
discovered,  about  125  to  250  to  a  cell.  These  granules  are  comparable  to 
those  found  in  the  goblet  cells,  and  may  be  interpreted  as  consisting  of 
mucin  or  some  preparatory  material  from  which  mucin  is  formed.  The 
granules  are  sensitive  to  reagents ;  addition  of  water  causes  them  to  swell  up 
and  disappear.  It  may  be  assumed  that  this  happens  during  secretion,  the  gran- 
ules becoming  converted  to  a  mucin-mass  which  is  extruded  from  the  cell. 

Action  of  Atropin,  Pilocarpin,  and  Nicotin  upon  the  Secretory- 
Nerves. — The  action  of  drugs  upon  the  salivary  glands  and  their  secretions 
belongs  properly  to  pharmacology,  but  the  effects  of  the  three  drugs  men- 
tioned are  so  decided  that  they  have  a  peculiar  physiological  interest.  Atro- 
pin in  small  doses  injected  either  into  the  blood  or  into  the  gland-duct 
prevents  the  action  of  the  cerebral  fibres  (tympanic  nerve  or  chorda  tympani) 
upon  the  glands.  This  effect  may  be  explained  by  assuming  that  the  atropin 
paralyzes  the  endings  of  the  cerebral  fibres  in  the  glands.  That  it  does  not 
act  directly  upon  the  gland-cells  themselves  seems  to  be  assured  by  the  inter- 
esting fact  that  with  doses  sufficient  to  throw  out  entirely  the  secreting  action 
of  the  cerebral  fibres,  the  sympathetic  fibres  are  still  effective  when  stimulated. 
Pilocarpin  has  directly  the  opposite  effect  to  atropin.  In  minimal  doses  it 
sets  up  a  continuous  secretion  of  saliva,  which  may  be  explained  upon  the 
supposition  that  it  stimulates  the  endings  of  the  secretory  fibres  in  the  gland. 
Within  certain  limits  these  drugs  antagonize  each  other — that  is,  the  effect  of 
pilocarpin  may  be  removed  by  the  subsequent  application  of  atropin  and  vice 
versa.  Nicotin,  according  to  the  experiments  of  Langley,2  prevents  the  action 
of  the  secretory  nerves,  not  by  action  on  the  gland-cells  or  the  endings  of  the 
nerve-fibres  round  them,  but  by  paralyzing  the  connections  between  the  nerve- 
fibres  and  the  ganglion  cells  through  which  the  fibres  pass  on  their  way  to  the 
gland.  If,  for  example,  the  superior  cervical  ganglion  is  painted  with  a  solu- 
tion of  nicotin,  stimulation  of  the  cervical  sympathetic  below  the  gland  will 
give  no  secretion;  stimulation,  however,  of  the  fibres  in  the  ganglion  or 
between  the  ganglion  and  gland  will  give  the  usual  effect.  By  the  use  of 
this  drug  Langley  is  led  to  believe  that  the  cells  of  the  so-called  submaxillary 
ganglion  are  really  intercalated  in  the  course  of  the  fibres  to  the  sublingual 
gland,  while  the  nerve-cells  with  which  the  submaxillary  fibres  make  con- 
nection are  found  chiefly  in  the  hilus  of  the  gland  itself. 

Paralytic  Secretion. — A  remarkable  phenomenon  in  connection  with  the 
salivary  glands  is  the  so-called  paralytic  secretion.  It  has  been  known  for  a 
long  time  that  if  the  chorda  tympani  is  cut  the  submaxillary  gland  after  a  cer- 
tain time,  one  to  three  days,  begins  t<>  secrete  slowly  and  the  secretion  contin- 

1  Journal  of  Physiology,  1889,  vol.  x.  p.  -133. 

2  Proceedings  of  (he  Royal  Society,   London,   1889,  vol.  xlvi.  j>.   123. 


230  AN  AMERICAN   TEXT-BOOK    OF  PHYSIOLOGY. 

ues  uninterruptedly  for  a  long  period — as  long,  perhaps,  as  several  weeks — and 
eventually  the  gland  itself  undergoes  atrophy.  Langley  l  states  that  section 
of  the  chorda  on  one  side  is  followed  by  a  continuous  secretion  from  the  glands 
on  botli  sides  ;  the  secretion  from  the  gland  of  the  opposite  side  he  designates 
:i-  tin'  antiparalytic  or  antilytic  secretion.  After  section  of  the  chorda  the 
iurve-fibres  peripheral  to  the  section  degenerate,  the  process  being  com- 
pleted within  a  few  days.  These  fibres,  however,  do  not  run  directly  to  the 
gland-cell ;  they  terminate  in  end-arborizations  round  sympathetic  nerve-cells 
placed  somewhere  along  their  course,  in  the  sub-lingual  ganglion,  for  instance, 
or  within  the  gland  substance  itself.  It  is  the  axons  from  these  second  nerve 
units  that  end  round  the  secreting  cells.  Langley2  has  accumulated  some 
facts  to  show  that  within  the  period  of  continuance  of  the  paralytic  secretion 
(5  to  6  weeks)  the  fibres  of  the  sympathetic  cells  are  still  irritable  to  stimula- 
tion. He  is  inclined  to  believe  therefore  that  the  continuous  secretion  is  due 
to  a  continuous  excitation,  from  some  cause,  of  the  local  nervous  mechanism 
in  the  gland.  On  the  other  hand,  it  is  possible  that  the  mere  cessation  of  the 
normal  action  of  the  chorda  fibres  is  followed  by  an  altered  metabolism  in  the 
gland  cells  of  such  a  nature  as  to  cause  a  continuous  feeble  secretion. 

Normal  Mechanism  of  Salivary  Secretion. — Under  normal  conditions 
the  flow  of  saliva  from  the  salivary  glands  is  the  result  of  a  reflex  stimulation 
of  the  secretorv  nerves.  The  sensory  fibres  concerned  in  this  reflex  must  be 
chiefly  fibres  of  the  glosso-pharyngeal  and  lingual  nerves  supplying  the  mouth 
and  tongue.  Sapid  bodies  and  various  other  chemical  or  mechanical  stimuli 
applied  to  the  tongue  or  mucous  membrane  of  the  mouth  will  produce  a  flow 
mi'  saliva.  The  normal  flow  during  mastication  must  be  effected  by  a  reflex 
of  this  kind,  the  sensory  impulse  being  carried  to  a  centre  and  thence  trans- 
mitted through  the  efferent  nerves  to  the  glands.  It  is  found  that  section  of 
the  chorda  prevents  the  reflex,  in  spite  of  the  fact  that  the  sympathetic  fibres 
are  still  intact.  No  satisfactory  explanation  of  the  normal  functions  of  the 
secretorv  fibres  in  the  sympathetic  has  yet  been  given.  Various  authors  have 
suggested  that  possibly  the  three  large  salivary  glands  respond  normally  to 
different  stimuli.  This  view  has  lately  been  supported  by  Pawlow,  who 
reports  that  in  the  dog  at  least  the  parotid  and  the  submaxillary  may  react 
quite  differently.  When  fistulas  were  made  of  the  ducts  of  these  glands  it 
was  found  that  the  submaxillary  responded  readily  to  a  great  number  of 
stimuli,  such  as  the  sight  of  food,  chewing  of  meats,  acids,  etc.  The  parotid, 
on  the  contrary,  seemed  to  react  only  when  dry  food,  dry  powdered  meat,  or 
bread  was  placed  in  the  mouth.  Dryness  in  this  case  seemed  to  be  the 
efficient  stimulus.  Since  the  How  of  saliva  is  normally  a  definite  reflex,  we 
should  expect  a  distinct  salivary  secretion  centre.  This  centre  has  been 
located  by  physiological  means  in  the  medulla  oblongata ;  its  exact  position 
is  not  clearly  defined,  but  possibly  it  is  represented  by  the  nuclei  of  origin  of 

1  Proceedings  of  the  Royal  Society,  London,  1885,  No.  236. 
1  Text-book  of  Physiology,  edited  by  Scbafer,  1898. 


SECRETION.  231 

the  secretory  fibres  which  leave  the  medulla  by  way  of  the  facial  and  glosso- 
pharyngeal nerves.  Owing  to  the  wide  connections  of  nerve-cells  in  the 
central  nervous  system  we  should  expect  this  centre  to  be  affected  by 
stimuli  from  various  sources.  As  a  matter  of  fact,  it  is  known  that  the 
centre  and  through  it  the  glands  may  be  called  into  activity  by  stimulation  of 
the  sensory  fibres  of  the  sciatic,  splanchnic,  and  particularly  the  vagus  nerves. 
So,  too,  various  psychical  acts,  such  as  the  thought  of  savory  food  and  the 
feeling  of  nausea  preceding  vomiting,  may  be  accompanied  by  a  flow  of  saliva, 
the  effect  in  this  case  being  due  probably  to  stimulation  of  the  secretion  centre 
by  nervous  impulses  descending  from  the  higher  nerve-centres.  Lastly,  the 
medullary  centre  may  be  inhibited  as  well  as  stimulated.  The  well-known 
effect  of  fear,  embarrassment,  or  anxiety  in  producing  a  parched  throat  may 
be  supposed  to  arise  in  this  way  by  the  inhibitory  action  of  nerve-impulses 
arising  in  the  cerebral  centres. 

Electrical  Changes  in  the  Gland  during  Activity. — It  has  been  shown 
that  the  salivary  as  well  as  other  glands  suffer  certain  changes  iu  electric 
potential  during  activity  which  are  comparable  in  a  general  way  to  the 
"  action  currents  "  observed  in  muscles  and  nerves  (see  section  on  Muscle  and 
Nerve).  The  theories  bearing  upon  the  causes  of  these  electrical  changes  are 
too  intricate  and  speculative  to  enter  upon  here.  The  reader  is  referred  to 
an  account  given  by  Biedcrmann  l  for  further  details. 

C.  Pancreas  ;   Glands  of  the  Stomach  and  Intestines. 

Anatomical  Relations  of  the  Pancreas. — The  pancreas  in  man  lies  in 
the  abdominal  cavity  behiud  the  stomach.  It  is  a  long,  narrow  gland,  its 
head  lying  against  the  curvature  of  the  duodenum  and  its  narrow  extremity 
or  tail  reaching  to  the  spleen.  The  chief  duct  of  the  gland  (duct  of  Wirsung) 
usually  opens  into  the  duodenum,  together  with  the  common  bile-duet,  about 
eight  to  ten  centimeters  below  the  pylorus.  In  some  cases,  at  least,  a  smaller 
duct  may  enter  the  duodenum  separately  somewhat  lower  down.  The  points  at 
which  the  ducts  of  the  pancreas  open  into  the  duodenum  vary  considerably  in 
different  animals.  For  instance,  in  the  dog  there  are  two  ducts,  the  larger  of 
which  enters  the  duodenum  separately  about  six  to  seven  centimeters  below 
the  pylorus,  while  in  the  rabbit  the  main  duct  opens  into  the  duodenum  over 
thirty  centimeters  below  the  pylorus.  The  nerves  of  the  pancreas  are  derived 
from. the  solar  plexus,  but  physiological  experiments  which  will  be  described 
presently  show  that  the  gland  receives  fibres  from  at  least  two  sources,  through 
the  vagus  nerve  and  through  the  sympathetic  system. 

Histological  Characters. — The  pancreas,  like  the  salivary  glands,  belongs 
to  the  compound  tubular  type.  The  cells  in  the  secreting  portions  of  the 
tubules,  the  so-called  alveoli,  belong  to  the  serous  or  albuminous  type,  and  are 
usually  characterized  by  the  fad  that  the  outer  portion  of  each  cell,  that  is, 
the  pari  toward  the  basement  membrane,  is  composed  of  a  clear  non-glandular 

1  Eleklrophysiologie,  Jena,  1895. 


232  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

substance  that  takes  stains  readily,  while  the  inner  portion  tnrned  toward 
the  lumen  is  rilled  with  conspicuous  granules.  In  addition  to  this  type  of 
cell,  which  is  the  characteristic  secreting  element  of  the  organ,  the  pancreas 
contains  a  number  of  irregular  masses  of  cells  of  a  different  character  (bodies 
of  Langerhans).  These  latter  cells  are  clear  and  small,  frequently  have  ill- 
defined  cell-bodies,  but  contain  nuclei  which  stain  readily  with  ordinary 
reagents.  By  some  these  eel  Is  are  supposed  to  be  immature  secreting  cells  of 
the  ordinary  pancreatic  type.  By  others  it  is  thought  that  they  are  a  separate 
type  of  cell  and  take  some  special  part  in  the  secretory  functions  of  the  pan- 
creas. Nothing  definite,  however,  is  known  as  to  their  physiological  import- 
ance. 

Composition  of  the  Pancreatic  Secretion. — The  pancreatic  secretion  is 
a  clear  alkaline  liquid  which  in  some  animals  (dog)  is  thick  and  mucilaginous. 
Its  phvsical  characters  seem  to  vary  greatly,  even  in  the  same  animal,  accord- 
ing to  the  duration  of  the  secretion  or  the  time  siuce  the  establishment  of  the 
fistula  by  which  it  is  obtained  (see  p.  300).  In  a  newly  made  fistula  in  the 
dog  the  secretion  is  thick,  but  in  a  permanent  fistula  it  becomes  much  thinner 
and  more  watery.  The  main  constituents  of  the  secretion  are  three  enzymes, 
a  large  percentage  of  proteid  material  the  exact  nature  of  which  is  not  known, 
some  fats,  soaps,  a  slight  amount  of  lecithin,  and  inorganic  salts.  The  strongly 
alkaline  nature  seems  to  be  due  chiefly  to  sodium  carbonate,  which  may 
be  present  in  amounts  equal  to  0.2  to  0.4  per  ceut.  The  three  enyzmes  are 
known  respectively  as  trypsin,  a  proteolytic  ferment ;  amylopsin,  a  diastatic 
ferment,  and  steapsin,  a  fat-splitiug  ferment.  The  action  of  these  enzymes 
in  digestion  is  described  in  the  section  on  Digestion. 

Action  of  the  Nerves  on  the  Secretion  of  the  Pancreas. — In  animals 
like  the  dog,  in  which  the  process  of  digestion  is  not  continuous,  the  secretion 
of  the  pancreas  is  also  supposed  to  be  intermittent.  A  study  of  the  flow  of 
secretion  as  observed  in  cases  of  pancreatic  fistula  indicates  that  it  is  connected 
with  the  beginning  of  digestion  in  the  stomach,  and  is  therefore  probably  a 
reflex  act.  Until  recently,  however,  little  direct  evidence  had  been  obtained 
of  the  existence  of  secretory  nerves.  Stimulation  of  the  medulla  was  known 
to  increase  the  flow  of  pancreatic  juice  and  to  alter  its  composition  as  regards 
the  organic  constituents,  but  direct  stimulation  of  the  vagus  and  the  sympa- 
thetic nerves  gave  only  negative  results.  Lately,  however,  Pawlow1  and  some 
of  his  students  have  been  able  to  overcome  the  technical  difficulties  in  the  way, 
and  have  given  what  seems  to  be  perfectly  satisfactory  proof  of  the  existence  of 
distinct  secretory  fibres  comparable  in  their  nature  to  those  described  for  the 
salivary  glands.  The  results  that  they  have  obtained  may  be  stated  briefly  as 
follow- :  Stimulation  of  either  the  vagus  nerve  or  the  sympathetic  causes,  after 
a  considerable  latent  period,  a  marked  flow  of  pancreatic  secretion.  The  failure 
of  other  experimenters  to  ^{  this  result  was  due  apparently  to  the  sensitive- 
ness of  the  gland  to  variations  in   its  blood-supply.      Either  direct  or  reflex 

'Paw-Lav  :  /'»  Bois-Reymond 's  Archiv  fur  Physiologie,  1893,  Suppl.  Bd.;  Mett:  Ibid.,  1894; 
Kudrewetsky:  Ibid.,  1894  ;  Pawlow:    Die  Arbeit  der  Verdauungsdriisen,  Wiesbaden,  1898. 


SECRETION.  233 

vasoconstriction  of  the  pancreas  prevents  the  action  of  the  secretory  nerves 
upon  it.  Thus  stimulation  of  the  sympathetic  gives  usually  no  effect  upon 
the  secretion,  because  vaso-constrictor  fibres  are  stimulated  at  the  same  time, 
but  if  the  sympathetic  nerve  is  cut  five  or  six  days  previously,  so  as  to  give 
the  vaso-constrictor  fibres  time  to  degenerate,  stimulation  will  cause,  after  a 
long  latent  period,  a  distinct  secretion  of  the  pancreatic  juice.  A  similar 
result  may  be  obtained  from  stimulating  the  undegenerated  nerve  if  mechani- 
cal stimulation  is  substituted  for  the  electrical. 

The  long  lateut  period  elapsing  between  the  time  of  stimulation  and  the 
effect  upon  the  flow  is  not  easily  understood.  The  authors  quoted  do  not 
give  an  entirely  satisfactory  explanation  of  this  curious  fact,  but  suggest  that 
it  may  be  due  to  the  presence  of  definite  inhibitory  fibres  to  the  gland,  which 
are  stimulated  simultaneously  with  the  secretory  fibres  and  thus  hold  the 
secretion  in  check  for  a  time.  The  existence  of  inhibitory  fibres  is  rendered 
probable  by  several  interesting  experiments,  for  an  account  of  which  the 
original  sources  must  be  consulted.1 

Histological  Changes  during  Activity. — The  morphological  changes  in 
the  pancreatic  cells  have  long  been  known  and  have  been  studied  satisfac- 
torily in  the  fresh  gland  as  well  as  in  preserved  specimens.  The  general 
nature  of  the  chauges  is  the  same  as  that  described  for  the  salivary  gland, 
and  is  illustrated  in  Figures  58,  59,  and  60.  If  the  gland  is  removed  from 
a  dog  which  has  been  fasting  for  about  twenty-four  hours  and  is  hardened 
in  alcohol  and  sectioned  and  stained,  it  will  be  found  that  the  cells  are  filled 
with  granules  except  for  a  narrow  zone  toward  the  basal  end,  which  is  marked 
off  more  clearly  because  it  stains  more  deeply  than  the  granular  portion  (Fig. 
58).     If,  on  the  contrary,  the  gland  is  taken  from  a  dog  which  had  been  fed 


Fig.  58.— Pancreas  of  the  dog  during  hungei :  preserved  in  alcohol  and  stained  in  carmine 

(after  Heidcnlmin). 

six  to  ten  hours  previously,  the  non-staining  granular  zone  is  much  reduced  in 
size,  while  the  clearer  non-granular  zone  is  enlarged  (Fig.  59).  The  increase 
in  size  of  the  non-gran  uiar  zone  does  not,  however,  entirely  compensate  for 

1  Pawlow:   Die  Arbeit  der   Venlaiuiv/jxiiriisen,  p.  78,  Wiesbaden,  1898. 


2:U 


AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY 


the  loss  of  the  granular  material,  so  that  the  cell  as  a  whole  is  smaller  in 
size  than  in  the  gland  from  the  fasting  animal.  It  seems  evident  that  during 
the  hours  immediately  following  a  meal — that  is,  at  the  time  when  we  know 


Fig.  59.— Pancreas  of  dog  during  first  stage  of  digestion  ;  alcohol,  carmine  (after  Heidenhain). 


that  the  gland  is  discharging  its  secretion,  the  granular  material  is  being  used 
up.  After  the  cessation  of  active  secretion — that  is,  during  the  tenth  to  the 
twentieth  hour  after  a  meal  in  the  case  of  a  dog  fed  once  in  twenty-four 


Fig.  60.— Pancreas  of  dog  during  second  stage  of  digestion;  alcohol,  carmine  (after  Heidenhain). 


hours — the  gland-cells  return  t<>  their  resting  condition  (Fig.  60).  New  gran- 
ules are  formed,  and  finally,  if  the  gland  is  left  unstimulated  they  fill  the 
entire  cell  except  for  a  narrow  margin  at  the  basal  end. 

Similar  results  are  reported  by  Kiiline1  and  Lea  from  observation^  made 
upon  the  pancreas  cells  in  a  living  rabbit.     In  the  inactive  gland  the  outlines 

1  Untertuchungen  aua  dem  phyriologischen  Institut  des  Universitats  Heidelberg,  1882,  Bd.  ii. 


SECRETION.  235 

of  the  individual  cells  are  not  clearly  distinguishable,  but  it  can  be  seen  that 
there  are  two  zones,  one  clear  and  homogeneous  on  the  side  toward  the  basement 
membrane,  and  one  granular  on  the  side  toward  the  lumen.  During  activity 
the  secretory  tubules  show  a  notched  appearance  corresponding  to  the  positions 
of  the  cells,  the  outlines  of  the  cells  become  more  distinct,  the  granular  zone 
becomes  smaller,  and  the  homogeneous  zone  increases  in  width.  It  should  be 
stated  also  that  in  this  latter  condition  the  basal  zone  of  the  cells  shows  a  dis- 
tinct striation.  From  these  appearances  we  must  believe  that,  as  in  the  case 
of  the  salivary  gland,  a  part  at  least  of  the  organic  material  of  the  secretion  is 
formed  from  the  granules  of  the  inner  zone,  and  that  the  granules  in  turn  are 
formed  within  the  cells  from  the  homogenous  material  of  the  outer  zone. 

Enzyme  and  Zymogen. — The  observations  just  described  indicate  that  the 
enzymes  of  the  pancreatic  secretion  are  derived  from  the  granules  in  the  cells, 
but  other  facts  show  that  the  granules  do  not  contain  the  enzymes  as  such,  but 
a  preparatory  material  or  mother-substance  to  which  the  name  zymogen 
(enzyme-maker)  is  given.  This  belief  rests  upon  facts  of  the  following  kind  : 
If  a  pancreas  is  removed  from  a  dog  that  has  fasted  for  twenty-four  hours, 
when,  as  we  have  seen,  the  cells  are  heavily  loaded  with  granules,  and  a  glycerin 
extract  is  made,  very  little  active  enzyme  will  be  found  in  it.  If,  however, 
the  gland  is  allowed  to  stand  for  twenty-four  hours  in  a  warm  spot  before  the 
extract  is  made,  or  if  it  is  first  treated  with  dilute  acetic  acid,  the  glycerin  ex- 
tract will  show  very  active  tryptic  or  amylolytic  properties.  Moreover,  if  an 
inactive  glycerin  extract  of  the  perfectly  fresh  gland  is  treated  by  various 
methods,  such  as  dilution  with  water  or  shaking  with  finely  divided  platinum- 
black,  it  becomes  converted  to  an  active  extract  capable  of  digesting  proteid 
material.  These  results  are  readily  explained  upon  the  hypothesis  that  the 
granules  contain  only  zymogen  material,  which  during  the  act  of  secretion,  or 
by  means  of  the  methods  mentioned,  may  be  converted  into  the  corresponding 
enzymes.  As  the  three  enzymes  of  the  pancreatic  secretion  seem  to  be  distinct 
substances,  one  may  suppose  that  each  has  it  own  zymogen  to  which  a  distinc- 
tive name  might  be  given.  The  zymogen  that  is  converted  into  trypsin  is 
frequently  spoken  of  as  trypsinogen. 

Normal  Mechanism  of  Pancreatic  Secretion. — Alter  the  establishment 
of  a  pancreatic  fistula  it  is  possible  to  study  the  flow  of  secretion  in  its  rela- 
tions to  the  ingestion  of  food.  Experiments  of  this  kind  have  Ween  made. 
They  show  that  in  animals  like  the  dog,  in  which  sufficient  food  may  be  taken 
in  a  single  meal  to  last  for  a  day,  the  flow  of  secretion  is  intimately  connected 
with  the  reception  of  food  into  the  stomach  and  its  subsequent  digestiv 
changes.  The  time  relations  of  the  secretion  to  the  ingestion  of  food  are 
shown  in  the  accompanying  chart  (Fig.  61).  The  secretion  begins  immedi- 
ately after  the  food  enters  the  stomach,  and  increases  in  velocity  up  to  a  cer- 
tain maximum  which  is  reached  some  time  between  the  first  and  the  third  hour 
after  the  meal.  The  velocity  then  diminishes  rapidly  to  the  fifth  or  sixth 
hour,  after  which  there  may  be  a  second  smaller  increase  reaching  its  maxi- 
mum about  the  ninth  to  the  eleventh  hour.     From  this  point  the  secretion 


•j:;.; 


AN  AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 


diminishes  in  quantity  to  the  sixteenth  or  seventeenth  hour,  when  it  has 
practically  reached  the  zero  point.  In  man,  in  whom  the  meals  normally 
occur  at  intervals  of  five  to  six  hours,  this  curve  of  course  would  have  a  dif- 
ferent form.     The  interesting  fact,  however,  that  the  secretion  starts  very  soon 


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Fig.  61.— <  iirvi-  of  the  secretion  of  pancreatic  juice  during  digestion.  The  figures  along  the  abscissa 
represent  hours  after  the  beginning  of  digestion ;  the  figures  along  the  ordinate  represent  the  quantity 
of  this  secretion  in  cubic  centimeters.    Curves  of  two  experiments  are  given  (after  Heidenhain). 

after  the  beginning  of  gastric  digestion  is  probably  true  for  human  beings,  and 
gives  strong  indication  that  the  secretion  is  a  reflex  act. 

Recently  a  number  of  experiments  have  been  reported  which  strengthen 
the  view  that  the  normal  secretion  of  the  pancreas  is  reflexly  excited  by 
stimuli  acting  upon  the  mucous  membrane  of  the  stomach  or  duodenum. 
Dolinsky,1  working  upon  dogs  by  Pawlow's  methods,  finds  that  acids  are 
particularly  effective  in  arousing  the  pancreatic  flow  ;  on  the  contrary,  alkalies 
in  the  stomach  diminish  the  pancreatic  secretion.  Dolinsky  believes  that  the 
normal  acidity  of  the  gastric  secretion  is  perhaps  the  most  effective  stimulus  to 
the  pancreatic  gland,  and  that  in  this  way  the  flow  of  gastric  juice  in  ordinary 
digestion  starts  the  pancreatic  gland  into  activity.  Whether  the  acid  acts 
after  absorption  into  the  blood,  or  stimulates  the  sensory  fibres  of  the  mucous 
membrane,  and  thus  reflexly  affects  the  pancreas  through  its  secretory 
nerves,  is  not  definitely  known,  but  the  probabilities  arc  in  favor  of  the 
latter  view.  It  is  probable  also  that  the  acid  acts  upon  the  sensory  fibres 
of  the  mucous  membrane  of  the  duodenum  rather  than  upon  the  gastric 
membrane. 

In  addition  to  acids,  it  has  been  found  that  oils  and  water  introduced  into  the 
stomach  also  cause  a  flow  of  pancreatic  juice,  the  stimulation  occurring  prob- 


1  Archives  des  Sciences  biologiques,  St.  Petersburg,  1895,  t.  iii.'p.  399. 


SECRETION.  237 

ably  after  these  substances  have  reached  the  duodenum.  Moreover,  Pawlow 
has  given  proof  that  the  secretion  of  the  pancreas  varies  in  both  quantity  and 
quality  with  the  nature  of  the  food.  Indeed,  there  seem  to  be  indications  of 
a  specific  relationship  between  the  food  and  the  composition  of  the  secretion, 
albuminous  food  giving  a  secretion  with  a  greater  digestive  action  on  pro- 
teids;  oily  foods,  a  secretion  with  a  larger  amount  of  fat-splitting  enzymes, 
and  so  on.  If  this  relationship  is  shown  to  exist,  it  forms  an  adaptation  whose 
mechanism  is  very  obscure.' 

Glands  of  the  Stomach. 

Histological  Characteristics. — The  glands  of  the  gastric  mucous  mem- 
brane belong  practically  to  the  type  of  simple  tubular  glands ;  for,  although 
two  or  more  of  the  simple  tubes  may  possess  a  common  opening  or  mouth, 
there  is  no  system  of  ducts  such  as  prevails  in  the  compound  glands,  and  the 
divergence  from  the  simplest  form  of  tubular  gland  is  very  slight.  Each  of 
these  glands  possesses  a  relatively  wide  mouth,  lined  with  the  columnar  epi- 
thelium found  on  the  free  surface  of  the  gastric  membrane,  and  a  longer,  nar- 
rower secreting  part,  which  penetrates  the  thickness  of  the  mucosa  and  is  lined 
by  cuboidal  cells.  The  glands  in  the  pyloric  end  of  the  stomach  differ  in  gen- 
eral appearance  from  those  in  the  fundic  end,  and  are  especially  characterized 
by  the  fact  that  they  possess  only  one  kind  of  secretory  cell,  while  the  fundic 
glands  contain  two  apparently  distinct  types  of  cells  (Fig.  64).  The  lumen  in  the 
latter  glands  is  lined  by  a  continuous  layer  of  short  cylindrical  cells  to  which 
Heidenhain  gave  the  name  of  chief-cells.  These  cells  are  apparently  concerned 
in  the  formation  of  pepsin,  the  proteolytic  enzyme  contained  in  the  gastric  secre- 
tion. In  addition  there  are  present  a  number  of  cells  of  an  oval  or  triangular 
shape  which  are  placed  close  to  the  basement  membrane  and  do  not  extend  quite 
to  the  main  lumen  of  the  gland.  These  cells  are  not  found  in  the  pyloric  glands ; 
they  are  known  by  various  names,  such  as  border-cells,  parietal  cells,  oxyntic 
cells,  etc.  The  last-mentioned  name  has  been  given  to  them  because  of  their 
supposed  connection  with  the  formation  of  the  acid  of  the  gastric  secretion.  The 
nature  and  function  of  these  border-cells  have  been  the  subject  of  much  discus- 
sion. From  the  histological  side  they  have  been  interpreted  as  representing 
either  immature  forms  of  the  chief-cell,  or  else  the  active  modificatioD  of  this 
cell.  Recent  work,  however,  seems  to  have  demonstrated  that  they  form  a 
specific  type  of  cell,  and  probably  therefore  have  a  specific  function.  An 
interesting  histological  fact  in  connection  with  the  parietal  cells  is  that,  in  the 
human  stomach  at  least,  they  frequently  contain  several  nuclei,  five  or  six, 
and  some  of  these  seem  to  be  derived  from  ingested  leucocytes.  They  are 
interesting  also  is  the  fact  that  they  contain  distinct  vacuoles  that  seem  to 
appear  some  time  after  digestion  has  begun,  reach  a  maximum  size,  and  then 
gradually  grow  smaller  and  finally  disappear.      Like  the  similar  phenomenon 

1  For  other  interesting  facts  bearing  upon  the  mechanism  of  pancreatic  secretion,  see  Walter : 
Archives  des  Sciences  biologiques,  1899,  t.  vii.  p.  1. 


238  AN   AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

described  for  other  gland-cells  (p.  226),  this  appearance  is  possibly  connected 
with  the  formation  of  the  secretion. 

The  duct  of  a  gastric  gland  was  formerly  supposed  to  be  a  simple  tube 
extending  the  length  of  the  gland.      A  number  of  recent  observers,  however, 
have  shown,  by  the  use  of  the  Golgi  stain,  that  this 
view  is  not  entirely  correct,  at  least  not  for  the  glands 
in  the  fundus  in  which  border-cells  are  present.      In 
these  glands  the  central  lumen  sends  offside  channels 
that  pass  to  the  border-cells  and  there   form  a  net- 
work  of  small   capillaries    lying   either    in   or  round 
the  cell.1      An    illustration  of  the  duct-system  of  a 
fundic  gland   is  given  in  Figure  62.     If  this  work 
i-  correct  it  would   seem   that  the  chief-cells  com- 
fig.  62.— Ducts  and  secretion     muiiicate  directly  with  the  central  lumen,  but  that 
capillars  '"  !'ari,",al  ,"';*•     the  border-cells  have  a  system  of  secretion  capillaries 

Oland  from  the  fundus  of  cat  s  _    J  l 

Btomach  (after  Langendorff  of  their  own,  resembling  in  this  respect  the  demi- 
lunes of  the  mucous  salivary  glands  (p.  220).  This 
fact  tends  to  corroborate  the  statement  previously  made,  that  the  border-cells 
form  a  distinct  type  of  cell  whose  function  is  probably  different  from  that 
of  the  chief-cells. 

Composition  of  the  Secretion  of  the  Gastric  Mucous  Membrane. — 
The  secretion  as  it  is  poured  out  on  the  surface  of  the  mucous  membrane  is 
composed  of  the  true  secretion  of  the  gastric  glands  together  with  more  or  less 
mucus,  which  is  added  by  the  columnar  cells  lining  the  surface  of  the  mem- 
brane and  the  mouths  of  the  glands.  In  addition  to  the  mucus,  water,  and 
inorganic  salts,  the  secretion  contains  as  its  characteristic  constituents  hydro- 
chloric acid  and  two  enzymes — namely,  pepsin  which  acts  upon  proteids,  and 
renuin  which  has  a  specific  coagulating  effect  upon  the  casein  of  milk.  For  an 
analysis  of  the  gastric  secretion  of  the  dog  see  p.  288.  According  to  Heiden- 
hain,2  the  secretion  from  the  pyloric  end  of  the  stomach  is  characterized  by  the 
absence  of  hydrochloric  acid,  although  it  still  contains  pepsin.  This  statement 
pests  upon  careful  experiments  in  which  the  pyloric  end  was  entirely  resected 
and  made  into  a  blind  pouch  which  was  then  sutured  to  the  abdominal  wall 
to  form  a  fistula.  In  this  way  the  secretion  of  the  pyloric  end  could  be  obtained 
free  from  mixture  with  the  secretion  of  any  other  part  of  the  alimentary  canal. 
By  this  means  Heidenhain  found  that  the  pyloric  secretion  is  an  alkaline  liquid 
containing  pepsin.  Tin-  fad  forms  the  strongest  evidence  for  Heidenhain's 
hypothesis  that  the  HC1  of  the  normal  gastric  secretion  is  produced  by  the 
"  border-cells"  of  the  fundic  glands  and  the  pepsin  by  the  "chief-cells,"  since 
HC1  is  formed  only  in  part-  of  the  stomach  containing  border-cells,  whereas 
the  pepsin  is  produced  in  the  pyloric  end.  where  only  chief-cells  are  present. 

Evidence  of  this  character  is  naturally  not  very  convincing,  and  the  hypoth- 

1  Laii^endorfi'  and  Laserstein  :  Pfluger's  Archiv  filr  die  gesammU  Physiologic,  1894,  Bd.  lv.  S. 
578. 

2  Archiv  fur  die  gesammti   Physiologic,  ls7s.   Bd,  xviii.  S.  169,  also  Bd.  xix. 


SECRETION.  239 

esis,  especially  that  part  connecting  the  border-cells  with  the  formation  of 
HO,  can  only  be  accepted  provisionally  until  further  investigation  confirms 
or  disproves  it.  It  should  be  stated  that  the  alkalinity  of  the  secretion  obtained 
from  the  pyloric  glands  by  Heideuhain's  method  has  been  attributed  by  some 
authors  to  the  abnormal  conditions  prevailing,  especially  to  the  section  of  the 
vagus  fibres  that  necessarily  results  from  the  operation.  Contejean l  asserts 
that  the  reaction  of  the  pyloric  membrane  under  normal  conditions  is  acid  in 
spite  of  the  absence  of  border-cells. 

Influence  of  the  Nerves  upon  the  Gastric  Secretion. — It  has  been  very 
difficult  to  obtain  direct  evidence  of  the  existence  of  extrinsic  secretory  nerves 
to  the  gastric  glands.     In  the  hands  of  most  experimenters,  stimulation  of  the 
vagi  and  of  the  sympathetics  has  given  negative  results,  and,  on  the  other 
hand,  section  of  these  nerves  does  not  seem  to  prevent  entirely  the  formation  of 
the  gastric  secretion.     There  are  on  record,  however,  a  number  of  observations 
that  point  to  a  direct  influence  of  the  central  nervous  system  on  the  secre- 
tion.    Thus  Bidder  and  Schmidt  found  that  in  a  hungry  dog  with  a  gastric 
fistula  (page  288)  the  mere  sight  of  food  caused  a  flow  of  gastric  juice ;  and 
Richet  reports  a  case  of  a  man  in  whom  the  oesophagus  was  completely  oc- 
cluded and  in  whom  a  gastric  fistula  was  established  by  surgical  operation. 
It  was  then  found  that  savory  foods  chewed  in  the  mouth  produced  a  marked 
flow  of  gastric  juice.     There  would  seem  to  be  no  clear  way  of  explaining  the 
secretions  in  these  cases  except  upon  the  supposition  that  they  were  caused  bv  a 
reflex  stimulation  of  the  gastric  mucous  membrane  through  the  central  nervous 
system.     These  cases  are  strongly  supported   by  some  recent   experimental 
work  on  dogs  by  Pawlow  2  and  Schumowa-Simanowskaja.     These  observers 
used  dogs  in  which  a  gastric  fistula  had  been  established,  and  in  which,  more- 
over, the  oesophagus  had  been  divided  in  the  neck  and  the  upper  and  lower 
cut  surfaces  brought  to  the  skin  and  sutured  so  as  to  make  two  fistulous 
openings.     In  these  animals,  therefore,  food  taken  into  the  mouth  and  subse- 
quently swallowed  escaped   to   the  exterior  through   the   upper  (esophageal 
fistula,  without   entering   the  stomach.     Nevertheless   this  "fictitious  meal," 
as  the  authors  designate  it,  brought  about  a  secretion  of  gastric  juice.     If  in 
such  animals  the  two  vagi  were  cut,  the  "fictitious  meal"  no  longer  caused 
a  secretion  of  the  gastric  juice,  and   this  fact  may  be  considered  as  showing 
that  the  secretion  obtained  when  the  vagi  were  intact  -was  due  to  a   reflex 
stimulation  of  the  stomach  through  these  nerves.     In  later  experiments8  from 
the  same  laboratory  the  secretion  caused  in  this  way  bv  the  act   of  eating  is 
designated  as  a  "  psychical  secretion,"  on  the  assumption,  for  which  consider- 
able evidence  is  given,  that  the  reflex  must  involve  psychical  factors  such   as 
the  sensations  accompanying  the  provocation  and  gratification  of  the  appetite. 
In  favorable  cases  the  fictitious  feeding  was  continued   for  as  long  as  five  to 
six  hours,  with  the  production  of  a  secretion  of  about  700  c.e.  of  pure  gastric 

1  Archives  de  Physiologie,  1S9'J,  p.  554. 

*  Du  Bois-Reymond! &  Archivjur  Physiologic,  1895,  S.  53. 

1  Die  Arbeit  der  Verdauungsdriisen,  Wiesbaden,  1898. 


240  AN   AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

juice.  Finally,  these  observers  were  able  to  show  that  direct  stimulation  of 
the  vagi  under  proper  conditions  causes,  after  a  long  latent  period  (four  and 
a  half  to  ten  minutes),  a  marked  secretion  of  gastric  juice.  The  long  latent 
period  is  attributed  to  the  simultaneous  stimulation  of  inhibitory  fibres. 

Taking  these  results  together,  we  must  believe  that  the  vagi  send  secretory 
fibres  to  the  gastric  glands,  and  that  these  fibres  may  be  stimulated  reflexly 
through  the  sensory  nerves  of  the  mouth,  and  probably  also  by  psychical 
states. 

Normal  Mechanism  of  Secretion  of  the  Gastric  Juice. — Our  knowl- 
edge of  the  means  by  which  the  flow  of  gastric  secretion  is  caused  during 
normal  digestion,  and  of  the  varying  conditions  which  influence  the  flow,  is 
as  vet  quite  incomplete.  The  notable  experiments  recently  made  by  Pawlow  ' 
and  his  pupils,  together  with  older  experiments  by  Heidenhain,2  have,  however, 
thrown  some  light  upon  this  difficult  problem,  and  have,  moreover,  opened 
the  way  for  further  experimental  study  of  the  matter.  Heidenhain  cut  out 
a  part  of  the  fundus  of  the  stomach,  converted  it  into  a  blind  sac,  and  brought 
one  end  of  the  sac  to  the  abdominal  wall  so  as  to  form  a  fistulous  opening  to 
the  exterior.  The  continuity  of  the  stomach  was  established  by  suturing  the 
cut  cnd>,  but  the  fundic  sac  was  completely  separated  from  the  rest  of  the 
alimentary  canal.  This  operation  has  since  been  modified  by  Pawlow  in  such 
a  way  that  the  isolated  fundic  sac  retains  its  normal  nerve  supply.  Heiden- 
hain found  that  under  these  conditions  the  ingestion  of  ordinary  food  caused 
a  secretion  in  the  isolated  and  empty  fundic  sac,  the  secretion  beginning 
fifteen  to  thirty  minutes  after  the  food  was  taken,  and  continuing  until  the 
stomach  was  empty.  The  ingestion  of  water  caused  a  temporary  secretion  in 
the  fundus,  while  indigestible  material  such  as  ligamentum  nucha?  gave  no 
secretion  at  all.  Heidenhain's  interpretation  of  these  experiments  as  applied 
to  normal  secretion  was  that  in  ordinary  digestion  we  must  distinguish 
between  a  primary  and  a  secondary  secretion.  The  primary  secretion  depends 
upon  the  mechanical  stimulus  of  the  ingested  food,  and  is  confined  to  the  spots 
directly  stimulated  ;  the  secondary  secretion  begins  after  absorption  from  the 
stomach  is  in  progress,  and  involves  the  whole  secreting  surface.  The  first 
part  of  this  theory  is  in  accord  with  a  belief  which  heretofore  has  been  very 
generally  held  by  physiologists,  namely,  that  the  gastric  glands  may  be  made 
to  secrete  by  direct  mechanical  excitation.  Pawlow  has  shown,  however,  by 
what  seem  to  be  most  convincing  experiments,  that  this  belief  is  erroneous. 
Mechanical  stimulation,  strong  or  weak,  circumscribed  or  general,  seems  to  be 
totally  without  effect  in  arousing  a  secretion.  Pawlow  has  been  led  by  his 
interesting  experiments  to  give  a  different  explanation  of  the  normal  mechan- 
ism of  secretion.  The  first  effect  of  eating  is  the  production  of  the  "  psychical 
secretion,"  before  referred  to.  This  secretion  is  effected  through  the  action 
of  secretory  fibres  in  the  vagus,  and  possibly  also  in  the  sympathetic  nerve.  It 
begins  usually  within  five  minutes,  is,  in  a  general  way,  proportional  in  amount 

1  Archives  des  Sciences  biologiques,  St.  Petersburg,  1895,  t.  iii.  p.  461 ;  t.  v.  p.  425. 
'Hermann's  Handbuch  der  Physiologie,  1883,  Bd.  v.  S.  114. 


SECRETION. 


241 


to  the  intensity  of  the  appetite  or  enjoyment  of  the  food,  and  may  last  for 
several  hours  even  though  the  aetnal  period  of  eating  has  been  short  (five  min- 
utes). It  is  this  secretion  that  first  acts  upon  the  food  received  into  the  stomach. 
Later  its  action  is  supplemented  by  an  augmented  secretion,  caused  by  stimuli 
of  a  chemical  nature  originating  in  the  food  ingested.  Some  foods  contain 
substances  ready  formed  that  are  capable  of  acting  in  this  way.  Investigation 
of  various  articles  of  diet  showed  that  meat  extracts,  juices,  and  soups  contain 
these  substances  in  largest  amounts.  Milk  and  aqueous  solutions  of  gelatin 
act  in  the  same  way,  although  less  powerfully.  Water  also,  if  in  sufficient 
quantity,  acts  as  a  direct  stimu- 
lant. Other  common  articles 
of  food,  such  as  bread  or  white 
of  egg,  do  not  contain  these 
stimulating  substances.  Food 
of  the  latter  character,  when 
introduced  directly  into  a  dog's 
stomach  through  a  fistula,  pro- 
vokes not  a  drop  of  secretion 
and  undergoes  no  digestion, 
if  it  has  been  introduced  in 
such  a  way  as  to  avoid  arous- 
ing the  psychical  secretion,  as, 
for  instance,  at  times  when  the 
animal  is  dozing.  If,  how- 
ever, this  latter  class  of  foods 
undergo  digestion,  as  would 
happen  in  normal  feeding  in 
consequence  of  the  action  of 
the  "  psychical  secretion,"  sub- 
stances capable  of  stimulating 
the  stomach  to  secretion  are 
developed,  and  their  action 
keeps  up  the  flow  of  secretion 
after  the  effect  of  the  psychical 
factor  has  become  weakened. 
The  nature  of  these  chemical 
stimuli  remains  entirely  undetermined.  Pawlow's  first  statement  that  pep- 
tone constituted  at  least  one  member  of  this  group  lie  now  finds  is  erroneous. 
It  is  assumed  that  these  substances  act  through  the  secretory  nerves,  and  it 
has  been  shown  also  that  other  substances  may  have  the  contrary  effeel  of 
retarding  or  inhibiting  the  gastric  secretion.  This  has  been  proved  tor  fats 
at  least.  Oils  of  various  kinds  decrease  the  secretion  of  gastric  juice,  while 
they  augment  the  pancreatic  secretion.  Another  mosl  suggestive  result  of 
Pawlow's  work  is  the  proof  that  the  quantity  and  characteristics  of  the  secre- 
tion vary  with  the  food.    Apparently  the  quantity  of  the  secretion  varies,  other 

Vol.  I.— 16 


f* 

•S'l 

2-2  a> 

■stive 
ver  in 
timet 

lity  in 
cent. 

Milk,         Meat,        Bread, 
600  c.c.        100  gr.          100  gr. 

Ml  o '" 

|& 

10 
8 
6 
4 
2 
0 

0.576 
0.528 
0.480 
0.432 
0.384 
0.336 
0.288 
0.240 
0.192 
0.144 
0.096 
0.048 
0 

18 
16 
14 
12 
10 
8 
6 
4 
2 
0 

\ 

• 

' 

' 

; 

\ 

i 

i 

\ 

; 

\ 

1 

\ 

f 

! 

' 

T 

\ 

i 

; 

I 

\ 

s 

J 

i 

~"  1 

■ 

1 

V 

t  Z34S6Y8?  Mini 



Quantity  of  secretioi 

i. 

;  .  ~y/ ' 

Ig 

■  1 

Fig.  63.— Diagram  showing  the  variation  in  quantity  of 
gastric  secretion  in  the  dog  after  a  mixed  meal:  also  the 
variations  In  acidity  and  In  digestive  power  (after  Ehigine). 


242  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

conditions  being  the  same,  with  the  amount  of  the  food  to  be  digested.  By 
some  means  the  apparatus  is  adjusted  in  this  respect  to  work  economically. 
Different  kinds  of  food  produce  secretions  varying  not  only  as  regards  quan- 
tity, but  also  in  their  acidity  and  digestive  action.  The  secretion  produced 
by  bread,  though  less  in  quantity  than  that  caused  by  meat,  possesses  a  greater 
digestive  action.  On  a  given  diet  the  secretion  will  assume  certain  charac- 
teristics, and  Pawlow  is  convinced  that  further  work  will  disclose  the  fact 
that  the  secretion  of  the  stomach  is  not  caused  normally  by  general  stimuli 
all  affecting  it  alike,  but  by  specific  stimuli  contained  in  the  food  or  produced 
during  digestion,  whose  action  is  of  such  a  kind  as  to  produce  the  secretion 
best  adapted  for  the  food  ingested. 

One  of  the  curves  showing  the  effect  of  a  mixed  diet  (milk,  GOO  cubic 
centimeters  ;  meat,  100  grams  ;  bread,  100  grams)  upon  the  gastric  secretion, 
as  determined  by  Pawlow's  method,  is  reproduced  in  Fig.  68.  It  will  be 
noticed  that  the  secretion  began  shortly  after  the  ingestion  of  the  food  (seven 
minutes),  and  increased  rapidly  to  a  maximum  that  was  reached  in  two  hours. 
After  the  second  hour  the  flow  decreased  rapidly  and.  nearly  uniformly  to 
about  the  tenth  hour.  The  acidity  rose  slightly  between  the  first  and  second 
hours,  and  then  fell  gradually.  The  digestive  power  showed  an  increase 
between   the   second  and   third   hours. 

Histological  Changes  in  the  Gastric  Glands  during-  Secretion. — The 
cells  of  the  gastric  glands,  especially  the  so-called  chief-cells,  show  distinct 
changes  as  the  result  of  prolonged  activity.  Upon  preserved  specimens  taken 
from  dogs  fed  at  intervals  of  twenty-four  hours,  Heidenhain  found  that  in  the 
fasting  condition  the  chief-cells  were  large  and  clear,  that  during  the  first  six 
hours  of  digestion  the  chief-cells  as  well  as  the  border-cells  increased  in  size, 
but  that  in  a  second  period  extending  from  the  sixth  to  the  fifteenth  hour,  the 
chief-cells  became  gradually  smaller,  while  the  border-cells  remained  large  or 
even  increased  in  size.  After  the  fifteenth  hour  the  chief-cells  increased  in 
size,  gradually  passing  back  to  the  fasting  condition  (see  Fig.  6*4). 

Langley  '  has  succeeded  in  following  the  changes  in  a  more  satisfactory 
way  by  observations  made  directly  upon  the  living  gland.  He  finds  that  the 
chief-cells  in  the  fasting  stage  are  charged  with  granules,  and  that  during 
digestion  the  granules  are  used  up,  disappearing  first  from  the  base  of  the 
cell,  which  then  becomes  filled  with  a  non-granular  material.  Observations 
similar  to  those  made  upon  the  pancreas  demonstrate  that  these  granules 
represent  in  all  probability  a  preliminary  material  from  which  the  gastric 
enzymes  are  made  during  the  act  of  secretion.  The  granules,  therefore,  as  in 
the  other  glands,  may  be  spoken  of  as  zymogen  granules,  the  preliminary 
material  of  the  pepsin  being  known  as  pepsinogen  and  that  of  the  rennin 
sometimes  as  pexinogen. 

Glands  of  the  Intestine. — At  the  very  beginning  of  the  intestine  in  the 
immediate  neighborhood  of  the  pylorus  is  found  a  small  area  of  mucous  mem- 
brane containing  distinct  tubular  glands,  known  usually  as  the  glands  of 
1  Journal  <>j  Physiology,  1880,  vol.  iii.  p.  269. 


SECRETION. 


243 


Brunner.  These  glands  resemble  closely  in  arrangement  those  of  the  pyloric 
end  of  the  stomach,  with  the  exception  that  the  tubular  duct  is  more  branched. 
The  secreting  cells  are  similar  to  those  of  the  pyloric  glands  of  the  stomach. 
Little  is  known  of  their  secretion.  According  to  some  authors  it  contains 
pepsin.  The  amount  of  secretion  furnished  by  these  glands  would  seem  to 
be  too  small  to  be  of  great  importance  in  digestion.     Throughout  the  length 


Fig.  64.— Glands  of  the  fundus  (dog)  :  A  and  A1,  during  hunger,  resting  condition  ;  />,  during  the  tir-t 
stage  of  digestion :  ''and  />,  the  second  stage  of  digestion,  showing  the  diminution  in  the  Bize  of  the 
"chief"  or  central  cells  (after  Heidenhain). 

of  the  small  and  large  intestine  the  well-known  crypts  of  Lieberkiihn 
are  found.  These  structures  resemble  the  gastric  glands  in  general  appear- 
ance, but  not  in  the  character  of  the  epithelium.  The  epithelium  lining  the 
crypts  is  of  t\\<>  varieties — the  goblet  cells,  whose  function  h  to  form  mucus, 
and  columnar  cells  with  a  characteristic  striated  border.  The  changes  in  the 
goblet  cells  during  secretion  and  the  probability  of  a  relationship  between  them 
and  the  neighboring  epithelial  cells  has  been  discussed  (see  p.  216). 
Whether  or  not  the  crypts  form  a  definite  secretion  has  Ween  much  debated. 
Physiologists  are  accustomed  to  speak  of  an  intestinal  juice,  "  succus  entericus," 
as  being  formed  by  the  glands  of  Lieberkiihn,  but  practically  uothing  is  known 
as  to  the  mechanism  of  the  secretion.  The  succus  entericus  itself,  however  it 
may  be  formed,  can  be  collected  by  isolating  small  loops  of  the  intestine  and 


244  AN   AMERICAN    TEXT-ROOK    OF  PHYSIOLOGY. 

bringing  the  ends  to  the  abdominal  wall  to  form  fistulous  openings.  The 
secretion  thus  obtained  contains  diastatie  and  also  inverting  ferments,  the  action 
of  which  is  described  on  p.  308.  Histologically,  the  cells  in  the  bottom  of 
the  crypts  do  not  possess  the  general  characteristics  of  secreting  cells. 

D.  Liver  ;  Kidney. 

The  liver  is  a  gland  belonging  to  the  compound  tubular  type.  The 
hepatic  cells  represent  the  secretory  cells  and  the  bile-ducts  carry  off  the 
external  secretion,  which  is  designated  as  bile.  In  addition  it  is  known  that 
the  liver-cells  occasion  important  changes  in  the  material  brought  to  them 
in  the  blood,  and  that  two  important  compounds,  namely,  glycogen  and  urea, 
are  formed  under  the  influence  of  these  cells  and  afterward  are  given  off  to 
the  blood-stream.  The  liver,  then,  furnishes  a  conspicuous  example  of  a 
gland  that  forms  simultaneously  an  external  and  an  internal  secretion.  In 
this  section  we  have  to  consider  only  certain  facts  in  relation  to  the  external 
secretion,  the  bile. 

Histological  Structure. — The  general  histological  relations  of  the  hepatic 
lobules  need  not  be  repeated  in  detail.  It  will  be  remembered  that  in  each 
lobule  the  hepatic  cells  arc  arranged  in  columns  radiating  from  the  central 
vein,  and  that  the  intralobular  capillaries  are  so  arranged  with  reference  to 
these  columns  that  each  cell  is  practically  brought  into  contact  with  a  mixed 
blood  derived  in  part  from  the  portal  vein  and  in  part  from  the  hepatic 
artery. 

As  a  gland  making  an  external  secretion,  the  relations  of  the  liver-cells  to 
the  ducts  and  to  the  nervous  system  are  important  points  to  be  determined. 
The  bile-ducts  can  be  traced  without  difficulty  to  the  fine  interlobular  branches 
running  round  the  periphery  of  the  lobules,  but  the  finer  branches  or  bile- 
capillaries  springing  from  the  interlobular  ducts  and  penetrating  into  the  in- 
terior of  the  lobules  have  been  difficult  to  follow  with  exactness,  especially  as  to 
their  connection  with  the  interlobular  ducts  on  the  one  hand,  aud  with  the 
liver-cells  on  the  other.  The  bile-capillaries  have  long  been  known  to  pene- 
trate  the  columns  of  cells  in  the  lobule  in  such  a  way  that  each  cell  is  in  con- 
tacl  with  a  bile-capillary  at  one  pointofits  periphery,  and  with  a  blood-capil- 
lary at  another,  the  bile-  and  blood-capillaries  being  separated  from  each  other 
by  a  portion  of  the  cell-snbstance.  But  whether  or  not  intracellular  blanches 
from  these  capillaries  actually  penetrate  into  the  substance  of  the  liver-cells 
ha-  been  a  matter  in  dispute.  Knppfer  contended  that  delicate  ducts  arising 
from  the  capillaries  enter  into  the  cells  and  end  in  a  small  intracellular  vesicle. 
As  this  appearance  was  obtained  by  forcible  injections  through  the  bile-duets, 
it  was  thought  by  many  to  be  an  artificial  product;  but  recent  observations 
with  staining  reagents  tend  to  substantiate  the  accuracy  of  Kuppfer's# obser- 
vations and  confirm  the  belief  that  normally  the  system  of  bile-duct-  begins 
within  the  liver-oil-  in  minute  channels  that  connect  directly  with  the  bile- 
capillaries. 

Two  questions  with  reference  to  the  bile-ducts  have  given  rise  to  considerable 


SECRETION.  245 

discussion  and  investigation  :  first,  the  relationship  existing  between  the  liver- 
cells  and  the  lining  epithelium  of  the  bile-duets  ;  second,  the  presence  or  ab- 
sence of  a  distinct  membranous  wall  for  the  bile-capillaries.  Different  opin- 
ions are  still  held  upon  these  points,  but  the  balance  of  evidence  seems  to  show 
that  the  bile-capillaries  have  no  proper  wall.  They  are  simply  minute  tubular 
spaces  penetrating  between  the  liver-cells  and  corresponding  to  the  alveolar  lu- 
men in  other  glands.  Where  the  capillaries  join  the  interlobular  ducts  the  liver- 
cells  pass  gradually  or  abruptly,  according  to  the  class  of  vertebrates  examined, 
into  the  lining  epithelium  of  the  ducts.  From  this  standpoint,  then,  the  liver- 
cells  are  homologous  to  the  secreting  cells  of  other  glands  in  their  relations  to 
the  general  lining  epithelium.  Several  observers  (MaCallum,1  Berkley,2  and 
Korolkow3)  have  claimed  that  they  are  able  to  trace  nerve-fibres  to  the 
liver-cells,  thus  furnishing  histological  evidence  that  the  complex  processes  oc- 
curring in  these  cells  are  under  the  regulating  control  of  the  central  nervous 
system.  According  to  the  latest  observers  (Berkeley,  Korolkow)  the  terminal 
nerve-fibrils  end  between  the  liver-cells,  but  do  not  actually  penetrate  the  sub- 
stance of  the  cells,  as  was  described  in  some  earlier  papers.  If  these  observa- 
tions prove  to  be  entirely  correct  they  would  demonstrate  the  direct  effect  of 
the  nervous  system  on  some  at  least  of  the  manifold  activities  of  the  liver- 
cells.  So  far  as  the  formation  of  the  bile  is  concerned  we  have  no  satisfactory 
phvsiological  evidence  that  it  is  under  the  control  of  the  nervous  system. 

Composition  of  the  Secretion. — The  bile  is  a  colored  secretion.  In 
most  carnivorous  animals  it  is  golden  red,  while  in  the  herbivora  it  is  green, 
the  difference  depending  on  the  character  and  quantity  of  the  pigments.  In 
man  the  bile  is  usually  stated  to  follow  the  carnivorous  type,  showing  a  red- 
dish or  brownish  color,  although  in  some  cases  apparently  the  green  predomi- 
nates. The  characteristic  constituents  of  the  bileare  the  pigments,  bilirubin  in 
carnivorous  bile  and  bilivcrdin  in  herbivorous  bile,  and  the  bile  acids  or  bile- 
salts,  the  sodium  salts  of  glycocholic  or  taurocholic  acid,  the  relative  proportions 
of  the  two  acids  varying  in  different  animals.  In  addition  there  is  present  a 
considerable  quantity  of  a  mucoid  nucleo-albumin,  a  constituent  which  is  QOl 
formed  in  the  liver-cells,  but  is  added  to  the  secretion  by  the  mucous  membrane 
of  the  bile-ducts  and  gall-bladder  ;  and  small  quantities  of  cholesterin,  lecithin, 
fats,  and  soaps.  The  inorganic  constituents  comprise  the  usual  salts — chlorides, 
phosphates,  carbonates  and  sulphates  of  the  alkalies  or  alkaline  earths.  Iron 
is  found  in  small  quantities,  combined  probably  as  a  phosphate.  The  secre- 
tion contains  also  a  considerable  though  variable  quantity  <>f  COa  gas,  held  in 
such  loose  combination  that  it  can  be  extracted  with  the  gas-pump  without  the 
addition  of  acid.  The  presence  of  this  constituent  serves  a-  an  indication  of 
the  extensive  metabolic  changes  occurring  in  the  liver-cells.  Quantitative 
analyses  of  the  bile  show  that  it  varies  greatly  in  composition  even  in  the  same 
species   of  animal.      Examples  of   this   variability   are  given    in   the  analyses 

1  MaCallum :  Quarterly  Journal  of  the  Microscopical  Sciences,  1887,  vol,  x.wii.  p.  189. 
■■*  Berkley  :    Anatomischer  Aruseiger,  1893,  Bd.  viii.  8.  769.  Korolkow:  Ibid.,  8.  750. 


240  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

quoted  in  the  section  on  Digestion  (p.  322),  where  a  brief  account  will  also  be 
found  of  the  origin  and  physiological  significance  of  the  different  constituents. 
The  Quantity  of  Bile  Secreted. — Owing  to  the  fact  that  a  fistula  of  the 
common  bile-duet  or  gall-bladder  may  be  established  upon  the  living  animal 
and  the  entire  quantity  of  bile  be  drained  to  the  exterior  without  serious  detri- 
ment t<>  the  animal's  lite,  we  possess  numerous  statistics  as  tothedailv  quantity 
of  the  secretion  formed.  Surgical  operations  upon  human  beings  (see  p.  321 
for  references),  made  necessary  by  occlusion  of  the  bile-passages,  have  furnished 
similar  data  for  man.  In  round  numbers  the  quantity  in  man  varies  from  500 
to  800  euliie  centimeters  per  day,  or,  taking  into  account  the  weight  of  the 
individuals  concerned,  about  8  to  16  cubic  centimeters  for  each  kilogram  of 
body-weight.  Observations  upon  the  lower  animals  indicate  that  the  secretion 
is  proportionally  greater  in  smaller  animals.  This  fact  is  clearly  shown  in  the 
following  table,  compiled  by  Heidenhain  '  for  three  herbivorous  animals: 

Sheep.  Rabbit.        Guinea-pig. 

Eatio  of  bile-weight  for  24  hours  to  body-weight   .    .    -  1 :  37.5  1 :  8.2  1 :  5.6 

Ratio  of  bile-weight  for  24  hours  to  liver-weight  .    .    .  1.507  : 1         4.0(54  : 1         4.467  : 1 

There  seems  to  be  no  doubt  that  the  bile  is  a  continuous  secretion,  although 
in  animals  possessing  a  gall-bladder  the  secretion  may  be  stored  in  this  reser- 
voir and  ejected  into  the  duodenum  only  at  certain  intervals  connected  with 
the  processes  of  digestion.  The  movement  of  the  bile-stream  within  the 
system  of  bile-ducts — that  is,  its  actual  ejection  from  the  liver,  is  also  probably 
intermittent.  The  observations  of  Copeman  and  Winston  on  a  human  patient 
with  a  biliary  fistula  showed  that  the  secretion  was  ejected  in  spirts,  owing 
doubtless  to  contraction-  of  the  muscular  walls  of  the  larger  bile-ducts.  But 
though  continuously  formed  within  the  liver-cells,  the  flow  of  bile  is  subject 
to  considerable  variations.  According  to  most  observers  the  activity  of  secre- 
tion is  definitely  connected  with  the  period  of  digestion.  Somewhere  from  the 
third  to  the  fifth  hour  after  the  beginning  of  digestion  there  is  a  very  marked 
acceleration  of  the  flow,  and  a  second  maximum  at  a  later  period,  ninth  to 
tenth  hour  (Hoppe-Seyler),  has  been  observed  in  dogs.  The  mechanism  con- 
trolling the  accelerated  How  during  the  third  to  the  fifth  hour  is  not  perfectly 
understood.  It  would  seem  to  be  correlated  with  the  digestive  changes  occur- 
ring  in  the  intestine,  but  whether  the  relationship  is  of  the  nature  of  a  reflex 
nervous  act,  or  whether  it  depends  on  increased  blood-flow  through  the  organ 
or  upon  some  action  of  the  absorbed  products  of  secretion  remains  to  be  deter- 
mined. It  has  been  shown  that  the  presence  of  bile  in  the  blood  acts  as  a 
stimulus  to  the  liver-cells,  and  it  is  highly  probable  that  the  absorption  of  bile 
from  the  intestine  which  occurs  during  digestion  serves  to  accelerate  the  secre- 
tion ;  but  this  circumstance  obviously  does  not  account  for  the  marked  increase 
observed  in  animals  with  biliary  fistulas,  since  in  these  cases  the  bile  does  not 
reach  the  intestine  at  all.  Therapeutically  various  substances  have  been 
stated  by  different  authors  to  act  as  true  cholagogues — that  is,  to  stimulate  the 
1  Hermann's  Handbuch  der  Physiologic,  Bd.  v.  Thl.  I,  S.  253. 


SECRETION.  'JIT 

secretion  of  bile.  Of  these  substances  the  <  >m-  whose  action  is  most  undoubted 
is  bile  itself  or  the  bile  acids.  When  given  as  dried  bile,  in  the  form  of 
pills,  a  marked  increase  in  the  flow  is  observed.' 

Relation  of  the  Secretion  of  Bile  to  the  Blood-flow  in  the  Liver. — 
Numerous  experiments  have  shown  that  the  quantity  of  bile  formed  by  the 
liver  varies  more  or  less  directly  with  the  quantity  of  blood  flowing  through 
the  organ.  The  liver-cells  receive  blood  from  two  sources,  the  portal  vein 
and  the  hepatic  artery.  The  supply  from  both  these  sources  is  probably  essen- 
tial to  the  perfectly  normal  activity  of  the  cells,  but  it  has  been  shown  that  bile 
continues  to  be  formed,  for  a  time  at  least,  when  either  the  portal  or  the  arterial 
supply  is  occluded.  However,  there  can  be  little  doubt  that  the  material  actually 
utilized  by  the  liver-cells  in  the  formation  of  their  external  and  internal  secre- 
tions is  brought  to  them  mainly  by  the  portal  vein,  and  that  variations  in  the 
quantity  of  this  supply  influences  directly  the  amount  of  bile  produced.  Thus, 
occlusion  of  some  of  the  branches  of  the  portal  vein  diminishes  the  secretion; 
stimulation  of  the  spinal  cord  diminishes  the  secretion,  since,  owing  to  the  large 
vascular  constriction  produced  thereby  in  the  abdominal  viscera,  the  quantity  of 
blood  in  the  portal  circulation  is  reduced  ;  section  of  the  spinal  cord  also  dimin- 
ishes the  flow  of  bile  or  may  even  stop  it  altogether,  since  the  result  of  such  an 
operation  is  a  general  paralysis  of  vascular  tone  and  a  general  fall  of  blood- 
pressure  and  velocity ;  stimulation  of  the  cut  splanchnic  nerves  diminishes  the 
secretion  because  of  the  strong  constriction  of  the  blood-vessels  of  the  abdom- 
inal viscera  and  the  resulting  diminution  of  the  quantity  of  the  blood  in  the 
portal  circulation  ;  section  of  the  splanchnics  alone,  however,  is  said  to  increase 
the  quantity  of  bile,  in  dogs,  since  in  this  case  the  paralysis  of  vascular  tone 
is  localized  in  the  abdominal  viscera.  The  effect  of  such  a  local  dilatation  of 
the  blood-vessels  would  be  to  diminish  the  resistance  alono-  the  intestinal 
paths,  and  thus  lead  to  a  greater  flow  of  blood  to  that  area  and  the  portal 
circulation. 

In  all  these  cases  one  might  suppose  that  the  greater  or  less  quantity  of 
bile  formed  depended  only  on  the  blood-pressure  in  the  capillaries  of  the  liver 
lobules — that  so  far  at  least  as  the  water  of  the  bile  is  concerned  it  is  produced 
by  a  process  of  filtration  and  rises  and  falls  with  the  blood-pressure.  That 
this  simple  mechanical  explanation  is  not  sufficient  seems  to  be  proved  by  the 
fact  that  the  pressure  of  bile  within  the  bile-ducts,  although  comparatively 
low,  may  exceed  that  of  the  blood  in  the  portal  vein. 

The  Existence  of  Secretory  Nerves  to  the  Liver. — The  numerous 
experiments  that  have  been  made  to  ascertain  whether  or  not  the  secretion 
of  bile  is  under  the  direct  control  of  secretory  nerves  have  given  unsatisfactory 
results.  The  experiments  are  difficult,  since  stimulation  of  the  nerves  supply- 
ing the  liver,  such  as  the  splanchnic,  is  accompanied  by  vaso-motor  changes 
which  alter  the  blood-flow  to  the  organ  and  thus  introduce  a  factor  that  in 
itself  influences  the  amount  of  the  secretion.  So  far  as  our  actual  knowledge 
goes,  the  physiological  evidence  is  against  the  existence  of  secretory  ncrve- 
1  Journal  of  Experimented  Medicine,  1897,  vol.  ii.  p.  4'.'. 


248  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

fibres  controlling  the  formation  of  bile.  On  the  other  hand,  there  are  some 
experiments,1  although  they  are  not  perfectly  conclusive,  which  indicate  that 
the  glycogen  formation  within  the  liver-cells  is  influenced  by  a  special  set  of 
glyco-seerehory  nerve-fibres.  This  fact,  however,  does  not  bear  directly  upon 
the  formation  of  bile. 

Motor  Nerves  of  the  Bile-vessels. — Doyon  2  has  recently  shown  that  the 
gall-bladder  as  well  as  the  bile-ducts  is  innervated  by  a  set  of  nerve-fibres 
comparable  in  their  general  action  to  the  vaso-constrictor  and  vaso-dilator 
fibres  of  the  blood-vessels.  According  to  this  author,  stimulation  of  the 
peripheral  end  of  the  cut  splanchnics  causes  a  contraction  of  the  bile-ducts 
and  gall-bladder,  while  stimulation  of  the  central  end  of  the  same  nerve,  on 
the  contrary,  brings  about  a  reflex  dilatation.  Stimulation  of  the  central  end 
of  the  vagus  nerve  causes  a  contraction  of  the  gall-bladder  and  at  the  same 
time  an  inhibition  of  the  sphincter  muscle  closing  the  opening  of  the  common 
bile-duct  into  the  duodenum.  These  facts  need  confirmation,  perhaps,  on  the 
pari  of  other  observers,  although  they  are  in  accord  with  what  is  known  of 
the  actual  movement  of  the  bile-stream.  The  ejection  of  bile  from  the  gall- 
bladder into  the  duodenum  is  produced  by  a  contraction  of  the  gall-bladder, 
and  it  is  usually  believed  that  this  contraction  is  brought  about  reflexly  from 
some  sensory  stimulation  of  the  mucous  membrane  of  the  duodenum  or 
stomach.  The  result  of  the  experiments  made  by  Doyon  would  indicate  that 
the  afferent  fibres  of  this  reflex  pass  upward  in  the  vagus,  while  the  efferent 
fibres  to  the  gall-bladder  run  in  the  splanchnics  and  reach  the  liver  through 
the  semilunar  plexus. 

Normal  Mechanism  of  the  Bile-secretion. — Bearing  in  mind  the  tact  that 
our  knowledge  of  the  secretion  of  bile  is  in  many  respects  incomplete,  and  that 
any  description  of  the  act  is  therefore  partly  conjectural,  wc  might  picture 
the  processes  concerned  in  the  secretion  and  ejection  of  bile  as  follows :  The 
bile  is  steadily  formed  by  the  liver-cells  and  turned  out  into  the  bile-capil- 
laries ;  its  quantity  varies  with  the  quantity  and  composition  of  the  blood 
flowing  through  the  liver,  but  the  formation  of  the  secretion  depends  upon 
the  activities  taking  place  in  the  liver-cells,  and  these  activities  are  independ- 
ent of  direct  nervous  control.  During  the  act  of  digestion  the  formation  of 
bile  is  increased,  owing  probably  to  a  greater  blood-flow  through  the  organ 
and  to  the  generally  increased  metabolic  activity  of  the  liver-cells  occasioned 
by  the  inflow  of  the  absorbed  products  of  digestion.  The  bile  after  it  gets 
into  the  bile-ducts  is  moved  onward  partly  by  the  accumulation  of  new  bile 
from  behind,  the  secretory  force  of  the  cells,  and  partly  by  the  contractions 
of  the  walls  of  the  bile-vessels.  It  is  stored  in  the  gall-bladder,  and  at  inter- 
vals during  digestion  is  forced  into  the  duodenum  by  a  contraction  of  the 
muscular  walls  of  the  bladder,  the  process  being  aided  by  the  simultaneous 
relaxation  of  a  sphincter-like  layer  of  muscle  that  normally  occludes  the 
bile-duct  :it  it-  opening  into  the  intestine;  both  these  last  acts  are  under  the 
control  of  a  nervous  reflex  mechanism. 

1  Morat  iiinl  Dufonrt:  Archives  de  Physiologie,  1  s04,  p.  371. 

2  Archives  de  Physiologic,  1894,  p.  19  ;  see  also  Oddi :  Arch.  tied,  de  Biologie,  t.  xxii.,  cvi. 


SECRETION.  249 

In  a  very  interesting  research  by   Bruno1  it  has  been  shown  that  the 
actual  passage  of  bile  into  the  intestine  is  occasioned,  reflexly  no  <1< ml >t ,  by 

the  passage  of  the  chyme  from  stomach  to  intestine.  As  long  as  the  stomach 
is  empty  no  bile  flows  into  the  duodenum  ;  the  flow  commences  when  the 
stomach  begins  to  empty  its  contents  into  the  intestine,  and  ceases  as  soon  as 
this  process  is  completed.  The  author  endeavored  to  ascertain  the  substances 
in  the  chyme  that  serve  as  the  stimulus  in  this  reaction.  As  far  as  his  experi- 
ments go,  they  show  that  fats  and  the  digested  products  of  proteids  (peptones 
and  proteoses)  are  the  most  efficient  stimuli.  Acids,  alkalies,  and  starch  or 
the  substances  formed  from  it  during  salivary  digestion  are  ineffective.  Pre- 
sumably the  fats  and  the  products  of  proteid  digestion  act  on  the  sensory 
fibres  of  the  duodenal  membrane. 

Effect  of  Complete  Occlusion  of  the  Bile-duct. — It  is  an  interesting 
fact  that  when  the  flow  of  bile  is  completely  prevented  by  ligation  of  the  bile- 
duct,  the  stagnant  liquid  is  not  reabsorbed  by  the  blood  directly,  but  by  the 
lymphatics  of  the  liver.  The  bile-pigments  and  bile-acids  in  such  cases  may 
be  detected  in  the  lymph  as  it  flows  from  the  thoracic  duct.  In  this  way  they 
get  into  the  blood,  producing  a  jaundiced  condition.  The  way  in  which  the 
bile  gets  from  the  bile-ducts  into  the  hepatic  lymphatics  is  not  definitelv  known, 
but  possibly  it  is  due  to  a  rupture,  caused  by  the  increased  pressure,  at  some 
point  in  the  course  of  the  delicate  bile-capillaries. 

Kidney. 

Histology. — The  kidney  is  a  compound  tubular  gland.  The  constituent 
uriniferous  tubules  composing  it  may  be  roughly  separated  into  a  secreting 
part  comprising  the  capsule,  convoluted  tubes,  and  loop  of  Henle,  and  a  col- 
lecting part,  the  so-called  straight  collecting-tube,  the  epithelium  of  which  is 
assumed  not  to  have  any  secretory  function.  Within  the  secreting  part  the 
epithelium  differs  greatly  in  character  in  different  regions;  its  peculiarities 
may  be  referred  to  briefly  here  so  far  as  they  seem  to  have  a  physiological 
bearing,  although  for  a  complete  description  reference  must  he  made  to  some 
work  on  Histology. 

The  arrangement  of  the  glandular  epithelium  in  the  capsule  with  reference 
to  the  blood-vessels  of  the  glomerulus  is  worthy  of  special  attention.  It  will 
be  remembered  that  each  Malpighian  corpuscle  consists  of  two  principal  parts, 
a  tuft  of  blood-vessels,  the  glomerulus,  and  an  enveloping  expansion  of  the 
uriniferous  tubule,  the  capsule.  The  glomerulus  is  a  remarkable  structure  (set- 
Fig.  65,  ^1).  It  consists  of  a  small  afferent  artery  which  after  entering  the 
glomerulus  breaks  up  into  a  number  of  capillaries,  which,  though  twisted 
together,  do  not  anastomose.  These  capillaries  unite  to  form  a  single  efferent 
vein  of  a  smaller  diameter  than  the  afferent  artery.  The  whole  structure, 
therefore,  is  not  an  ordinary  capillary  area,  but  a  rete  mirabile,  and  the  phys- 
ical factors  are  such  that  within  the  capillaries  of  the  rete  there  must  he  a 
greatly  diminished  velocity  of  the  blood-stream,  owing  to  the  great  increase 
1  Archives  des  sciences  biologiques,  18'J9,  t.  vii.  p.  87. 


I'.-.u 


AN    AMERICAN    TEXT-BOOK    OF   PHYSIO/A OG  V. 


in  the  width  of  the  stream-bed,  and  a  high  blood-pressure  as  compared  with 
ordinary  capillaries.  Surrounding;  this  glomerulus  is  the  double- walled  capsule. 
<  me  wall  of  the  capsule  is  closely  adherent  to  the  capillaries  of  the  glomerulus; 
it  not  only  covers  the  structure  closely,  but  dips  into  the  interior  between  the 
small  lobules  into  which  the  glomerulus  is  divided.  This  layer  of  the  capsule 
is  composed  of  flattened  endothelial-like  cells,  the  glomerular  epithelium,  to 
which  great  importance  is  new  attached  in  the  formation  of  the  secretion.  It 
will  benoticed  that  between  the  interior  of  the  blood-vessels  of  the  glomerulus  and 


Fig.  65.— Portions  of  the  various  divisions  of  the  uriniferous  tubules  drawn  from  sections  of  human 
kidney:  .1,  Malpighian  body ;  x,  squamous  epithelium  lining  the  capsule  and  reflected  over  the  glomer- 
ulus ;  //,  e,  a  Hi  rent  and  efferent  vessels  of  the  tuft;  e,  nuclei  of  capillaries;  n,  constricted  neck  marking 
passage  of  capsule  into  convoluted  tubule ;  B,  proximal  convoluted  tubule :  C,  irregular  tubule;  D  and 
F,  spiral  tubules  ;  E,  ascending  limb  of  Henle's  loop;  G,  straight  collecting  tubule  (Piersol). 

the  cavity  of  the  capsule,  which  is  the  beginning;  of  the  uriniferous  tubule,  there 
are  interposed  only  two  very  thin  layers,  namely,  the  epithelium  of  the  capil- 
lary wall  and  the  glomerular  epithelium.  The  apparatus  would  seem  to  afford 
most  favorable  conditions  for  filtration  of  the  liquid  parts  of  the  blood.  The 
epithelium  clothing  the  convoluted  portion-  of  the  tubule,  including  under  this 
designation  the  so-called  irregular  and  spiral  portions  and  the  loop  of  Henle,  is 
of  a  character  quite  different  from  that  of  the  glomerular  epithelium  (Fig.  65,  B, 
C,  D,  E,  F,  G).  The  cells,  speaking  generally,  are  cuboidal  or  cylindrical,  proto- 
plasmic,  and  granular  in  appearance;  on  the  side  toward  the  basement  mem- 
brane they  often  show  a  peculiar  >t  nation,  while  on  the  lumen  side  the  extreme 
periphery  presents  a  compact  border  which  in  some  cases  shows  a  cilia-like 
itriation.  These  cells  have  the  general  appearance  of  active  secretory  struc- 
tures, and  recent  theories  of  urinary  secretion  attribute  this  importance  to  them. 
Composition  of  Urine. — The  chemical  composition  of  the  urine  is  very 
complex,  as  we  should  expect  it  to  be  when  we  remember  that  it  contains  most 
of  the  end-products  of  the  varied  metabolism  of  the  body,  its  importance  in 
this  respect  being  greater  than  the  other  excretory  organs  such  as  the  lungs,  skin, 
and  intestine.  The  secretion  is  a  yellowish  liquid  which  in  carnivorous  ani- 
mal- and  in  man  has  normally  an  acid  reaction,  owing  to  the  presence  of  acid 


SECRETION.  251 

salts  (acid  sodium  and  acid  calcium  phosphate),  and  an  average  specific  gravity 
of  1017  to  1020.  The  quantity  formed  in  twenty-four  hours  is  about  1200  to 
1700  cubic  centimeters.  In  the  very  young  the  amount  of  urine  formed  is 
proportionately  much  greater  than  in  the  adult.  The  normal  urine  contains 
about  3.4  to  4  per  cent,  of  solid  matter,  of  which  over  half  is  organic  mate- 
rial. Among  the  important  organic  constituents  of  the  urine  are  the  follow- 
ing :  urea,  uric  acid,  hippuric  acid,  xanthin,  hypoxanthin,  guanin,  creatinin 
and  aromatic  oxy-  acids  (para-oxyphenyl  propionic  acid  and  para-oxyphenyl 
acetic  acid,  as  simple  salts  or  combined  with  sulphuric  acid) ;  phenol,  paracre- 
sol,  pyrocatechin  and  hydrochinon,  these  four  substances  being  combined  with 
sulphuric  or  glycuronic  acid;  iudican  or  indoxyl  sulphuric  acid;  skatol  sul- 
phuric acid  ;  oxalic  acid  ;  sulphocyanides,  etc.  These  and  other  organic  con- 
stituents occurring  under  certain  conditions  of  health  or  disease  in  various 
animals,  are  of  the  greatest  importance  in  enabling  us  to  follow  the  metab- 
olism of  the  body.  Something  as  to  their  origin  and  significance  will  be 
found  in  the  section  on  Nutrition,  while  their  purely  chemical  relations 
are  described  in  the  section  on  Chemistry. 

Among  the  inorganic  constituents  of  the  urine  may  be  mentioned  sodium 
chloride,  sulphates,  phosphates  of  the  alkalies  and  alkaline  earths,  nitrates,  and 
carbon  dioxide  gas  partly  in  solution  and  partly  as  carbonate.  In  this  sect  inn 
we  are  concerned  only  with  the  general  mechanism  of  the  secretion  of  urine, 
and  in  this  connection  have  to  consider  mainly  the  water  and  soluble  inorganic 
salts  and  the  typical  nitrogenous  excreta,  namely,  urea  and  uric  acid. 

The  Secretion  of  Urine. — The  kidueys  receive  a  rich  supply  of  nerve- 
fibres,  but  most  histologists  have  been  unable  to  trace  any  connection  between 
these  fibres  and  the  epithelial  cells  of  the  kidney  tubules.  Berkley  '  has,  how- 
ever, described  nerve-fibres  passing  through  the  basement  membrane  and 
ending  between  the  secretory  cells. 

The  majority  of  purely  physiological  experiments  upon  direct  stimulation  of 
the  nerves  going  to  the  kidney  are  adverse  to  the  theory  of  secretory  fibres,  the 
marked  effects  obtained  in  these  experiments  being  all  explicable  by  the  changes 
produced  in  the  blood-flow  through  the  organ.  Two  general  theories  of  urinary 
secretion  have  been  proposed.  Ludwig  held  that  the  urine  is  formed  by  the 
simple  phvsical  processes  of  filtration  and  diffusion.  In  the  glomeruli  the 
conditions  are  most  favorable  to  filtration, and  he  supposed  that  in  these  struc- 
tures water  filtered  through  from  the  blood,  carrying  with  it  not  only  the  in- 
organic salts,  but  also  the  specific  elements  (urea)  of  the  secretion.  There  was 
thus  formed  at  the  beginning  of  the  uriniferous  tubules  a  complete  bul  diluted 
urine,  and  m  the  subsequent  passage  of  this  Liquid  along  the  convoluted  tubes 
it  became  concentrated  by  diffusion  with  the  lymph  surrounding  the  outside 
of  the  tubules.  S<>  far  as  the  latter  part  of  this  theory  is  concerned  it  has 
not  been  supported  by  actual  experiments;  recent  histological  work  (see  below) 
seems  to  indicate  that   the  epithelial  cells  of  the  convoluted  tubules  have  a 

1  The  Johns  Hopkins  Hospital  Bulletin,  vol.  iv.,  No.  28, p.  1. 


252  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

distinct  secretory  function,  and  that  tiny  give  material  to  the  secretion  rather 
than  take  from  it. 

Bowman's  theory  of  urinary  secretion,  which  has  since  been  vigorously 
supported  and  extended  by  Heidenhain,  was  based  apparently  mainly  on  his- 
tological grounds.  It  assumes  that  in  the  glomeruli  water  and  inorganic  salts 
are  produced,  while  the  urea  and  related  bodies  are  eliminated  through  the 
activity  of  the  epithelial  cells  in  the  convoluted  tubes. 

Elimination  <>/  Urea  <ni<l  Related  Bodies. — Numerous  facts  have  been 
discovered  which  tend  to  support  the  latter  part  of  Bowman's  theory — namely, 
the  participation  of  the  cells  of  the  convoluted  tubules  in  the  secretion  of  the 
specific  nitrogenous  element.-.  In  birds  the  main  nitrogenous  element  of  the 
Becretion  is  uric  acid  instead  of  urea,  and  it  is  possible,  owing  to  the  small  solu- 
bility of  the  urates,  to  see  them  as  solid  deposits  in  microscopic  sections  of  the 
kidney.  When  the  ureters  are  ligated  the  deposition  of  the  urates  in  the  kid- 
ney may  Income  so  great  as  to  give  the  entire  organ  a  whitish  appearance. 
Nevertheless  histological  examination  of  a  kidney  in  this  condition  shows  that 
the  urates  are  found  always  in  the  tubes  and  never  in  the  Malpighian  corpus- 
cles. From  this  result  we  may  conclude  that  the  uric  acid  is  eliminated 
through  the  epithelial  cells  of  the  tubes.  Heidenhain  has  shown  by  a  striking 
series  of  experiments  that  the  cells  of  the  tubes  possess  au  active  secretory 
power.  In  these  experiments  a  solution  of  indigo-carmine  was  injected  into 
the  circulation  of  a  living  animal  after  its  spinal  cord  had  been  cut  to  reduce 
the  blood-pressure  and  therefore  the  rapidity  of  the  secretion.  After  a  certain 
interval  the  kidneys  were  removed  and  the  indigo-carmine  precipitated  in  situ 
in  the  kidney  by  injecting  alcohol  into  the  blood-vessels.  It  was  found  that 
the  pigment  granules  were  deposited  in  the  convoluted  tubes,  but  never  in  the 
Malpighian  corpuscles. 

Still  further  proof  of  definite  secretory  functions  on  the  part  of  the  cells 
of  the  tubules  is  given  by  the  results  of  recent  histological  work  upon  the 
changes  in  the  cells  during  activity.  Van  der  Stricht,'  Disse,2and  Trambusti 3 
describe  definite  morphological  changes  in  the  epithelial  cells  of  the  convoluted 
tubes  and  ascending  loop  of  Henle  which  they  connect  with  the  functional 
activity  of  the  cells.  The  details  of  the  descriptions  differ,  but  the  authors 
agree  in  finding  that  the  material  of  the  secretion  collects  in  the  interior  of  the 
cell  to  form  a  vesicle  which  is  afterward  discharged  into  the  lumen  of  the  cell. 
According  to  Disse  the  inactive  cells  are  small  aud  granular,  and  toward  the 
lumen  .-how  a  striated  border  of  minute  processes,  while  the  lumen  of  the  tube 
is  relatively  wide.  As  the  fluid  secretion  accumulates  in  the  cells  it  may  be 
distinguished  as  a  clear  vesicular  area  near  the  nucleus.  The  cells  enlarge 
ami  project  toward  the  lumen,  which  becomes  smaller;  the  striated  border  dis- 
appears.     Finally  the  swollen  cells  fill  the  entire  canal,  and  the  liquid  secre- 

1  ( 'omptes  rendus,  1891,  and  Travail  du  Laboratoire  d? Histologic  <l>'  /'  UniversiU  de  Oand,  1892. 

2  Referate  und  Beiirdge  zur  Analomie  and  Entvrickdungsgesehichte  (anatomische  Hefte),  Merkel 
and  Bonnet,  1893. 

3  Archives  Ualiennes  de  liiologie,  1898,  t.  30,  p.  426. 


sec  i  urn  ox.  253 

tion  is  emptied  from  the  cells  by  filtration.     Van  der  Stricht  believes  that  the 

vesicles  rupture  and  thus  empty  into  the  lumen.  In  longitudinal  sections 
various  stages  in  the  process  may  be  seen  scattered  along  the  length  of  a 
single  tubule. 

Secretion  of  the  Water  and  Salts. — There  seems  to  be  no  question  that  the 
elimination  of  water  together  with  inorganic  salts,  and  probably  still  other 
soluble  constituents,  takes  place  chiefly  through  the  glomerular  epithelium. 
This  supposition  is  made  in  both  the  general  theories  that  have  been  men- 
tioned. It  has,  however,  long  been  a  matter  of  controversy,  in  this  as  in 
other  glands,  whether  the  water  is  produced  by  simple  filtration  or  whether 
the  glomerular  epithelium  takes  an  active  part  of  some  character  in  setting  up 
the  stream  of  water.  The  problem  is  perhaps  simpler  in  this  case  than  in  the 
salivary  glands,  since  the  direct  participation  of  secretory  nerves  in  the  process 
is  excluded.  Ou  the  filtration  theory  the  quantity  of  urine  should  vary 
directly  with  the  blood-pressure  in  the  glomerulus.  This  relationship  has 
been  accepted  as  a  crucial  test  of  the  validity  of  the  filtration  theory,  and 
numerous  experiments  have  been  made  to  ascertain  whether  it  invariably 
exists.  Speaking  broadly,  any  general  rise  of  blood-pressure  in  the  aorta  will 
occasion  a  greater  blood-flow  and  greater  pressure  in  the  glomerular  vessels 
provided  the  kidney  arteries  themselves  are  not  simultaneously  constricted  to 
a  sufficient  extent  to  counteract  this  favorable  influence  ;  whereas  a  general  fall 
of  pressure  should  have  the  opposite  influence  both  on  pressure  and  velocity  of 
flow.  It  has  been  shown  experimentally  that  if  the  general  arterial  pressure 
falls  below  40  or  50  millimeters  of  mercury,  as  may  happen  after  section  of 
the  spinal  cord  in  the  cervical  region,  the  secretion  of  the  urine  will  be  greatly 
slowed,  or  suspended  completely.  Constriction  of  the  small  arteries  in  the 
kidney,  whether  effected  through  its  proper  vaso-constrictor  nerves  or  by  par- 
tially clamping  its  arteries,  causes  a  diminution  in  the  secretion  and  at  the 
same  time  in  all  probability  a  fall  of  pressure  within  the  glomeruli  and  a 
diminution  in  the  total  flow  of  blood.  On  the  other  hand,  dilatation  of  the 
arteries  of  the  kidney,  whether  produced  through  its  vaso-dilator  fibres  or  by 
section  or  inhibition  of  its  constrictor  fibres,  augments  the  flow  of  urine  and 
at  the  same  time  probably  increases  the  pressure  within  the  glomerular  capil- 
laries, and  also  the  total  quantity  of  blood  flowing  through  them  in  a  unit  of 
time.  From  these  and  other  experimental  facts  it  is  evident  that  the  amount 
of  secretion  and  the  amount  of  pressure  within  the  glomerular  vessels  do  often 
vary  together,  and  this  relationship  has  been  used  to  prove  that  the  water  of 
the  secretion  is  obtained  by  filtration  from  the  blood-plasma.  lint  it  will  be 
observed  that  the  quantity  of  secretion  varies  not  only  with  the  pressure  of 
the  blood  within  tin;  glomeruli,  but  also  with  the  quantity  of  blood  (lowing 
through  them.  Ileidenhain  has  insisted  that  it  is  this  latter  factor  and  not 
the  intracapillary  pressure  which  determines  the  quantity  of  water  secreted. 
He  believes  that  the  glomerular  epithelial  cells  possess  the  property  of  actively 
secreting  water,  and  that  they  are  not  simply  passive  fillers;  that  the  forma- 
tion, in   other  words,  is   not    a  simple   mechanical  process,  bin  a  more  complex 


254  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

one  depending  upon  the  living  structure  and  properties  of  the  epithelial  cells. 
In  support  of  this  view  he  quotes  the  fact  that  partial  compression  of  the 
renal  veins  quickly  slows  or  stops  altogether  the  flow  of  urine.  Compression 
of  the  veins  should  raise  the  pressure  within  the  vessels  of  the  glomeruli,  and 
upon  the  filtration  hypothesis  should  increase  rather  than  diminish  the  secre- 
tion. It  has  been  shown  also  that  if  the  renal  artery  is  compressed  for  a 
short  time  so  as  to  completely  shut  off  the  blood-flow  to  the  kidney  the 
secretion  is  not  only  suspended  during  the  closure  of  the  arteries  but  for  a 
long  lime  after  the  circulation  is  re-established.  According  to  Tiegerstedt, 
if  the  renal  artery  is  ligated  for  only  half  a  minute  the  activity  of  the 
kidney  is  suspended  for  three-quarters  of  an  hour.  This  fact  is  difficult  to 
understand  if  the  glomerular  epithelium  is  regarded  simply  as  a  filtering  mem- 
brane, but  it  is  explicable  upon  the  hypothesis  that  the  epithelial  cells  are 
actively  concerned  in  the  production  of  the  water. 

The  uncertainty  as  to  the  mechanism  of  production  of  the  water  and  salts 
renders  it  difficult  to  give  a  theoretical  explanation  of  the  action  of  diuretics. 
VTarious  -aline  substances,  such  as  NaCl  and  KXOs,  increase  the  flow  of  urine. 
According  to  Starling,1  these  substances  increase  the  bulk  of  water  in  the 
blood  by  drawing  water  from  the  tissues.  A  condition  of  hydraemic  plethora. 
ensues,  causing  a  greater  volume  of  blood  in  the  kidney  capillaries  and  a  rise 
of  capillary  pressure,  conditions  that  favor  greater  filtration  and  account  in 
part  for  the  increased  amount  of  urine.  Experiments  seem  to  show,  however, 
that  the  condition  of  hydraemic  plethora  passes  off  before  the  increased  secre- 
tion of  urine  ceases,  so  that  the  diuretic  action  of  the  salts  is  not  due  to  this 
factor  alone.  The  adherents  of  the  filtration  theory  assume  that  in  addition 
the  -alts  cause  a  vaso-dilatation  in  the  kidney,  and  thus  produce  a  rise  in 
blood-pressure  in  the  glomeruli.  According  to  the  other  point  of  view,  these 
substances  may  be  considered  as  having  a  specific  stimulating  effect  upon  the 
glomerular  epithelium.  So  the  action  of  caffein  may  be  referred  either  to  a 
specific  action-  on  the  secreting  cells  or  possibly  to  an  indirect  effect  exerted 
through  the  circulation  of  the  kidney.  It  seems  clear  that  at  present  we  arc 
not  justified  in  asserting  more  than  that  the  glomeruli  control  in  some  way  the 
production  of  the  water  and  salts  of  the  secretion.  The  extent  of  the  activity 
seems  to  be  correlated  with  the  quantity  of  blood  flowing  through  the 
glomeruli. 

It  must  be  borne  in  mind,  however,  that  some  water  and  probably  also 
some  of  the  inorganic  salts  are  secreted  at  other  part-  of  the  tubule  along 
with  the  nitrogenous  wastes.  It  is  of  interest  to  add  that  the  most  important 
of  the  abnormal  constituents  of  the  urine  under  pathological  conditions,  such 
as  the  albumin  in  albuminuria,  the  haemoglobin  in  haemoglobinuria,  and  the 
sugar  in  glycosuria,  seem  likewise  to  escape  from  the  blood  into  the  kidney 
tubule-  through  the  glomerular  epithelium. 

1  Journal  of  Physiology,  1899,  vol.  24,  i>.  :!17. 

Von  Schr ler :   Archiv.  fur  exper.   Pathologie  and  Pharmakol .,  Bd.  xxiv.  S.   85;  and 

Dreser,  Ibid.,  1892,  Bd.  xxix.  S.  303. 


SECRETION.  255 

The- normal  stimulus  to  the  epithelial  cells  of  the  convoluted  tubules, 
using  the  term  convoluted  to  include  the  actively  secreting  part-,  seems  to 
be  the  presence  of  urea  and  related  substances  in  the  blood  (lymph).  That 
the  elimination  of  the  urea  is  not  a  simple  act  of  diffusion  seems  to  be  clearly 
shown  by  the  fact  that  its  percentage  in  the  blood  is  much  less  than  in  the 
urine.  In  some  way  the  urea  is  selected  from  the  blood  and  passed  into  the 
lumen  of  the  tubule,  and  although  we  have  microscopic  evidence  that  tins 
process  involves  active  changes  in  the  substance  of  the  cells,  there  is  no  ade- 
quate  theory  of  the  nature  of  the  force  which  attracts  the  urea  from  the  sur- 
rounding lymph.  The  whole  process  must  be  rapidly  effected  by  the  cell, 
since  there  is  normally  no  heaping  up  of  urea  in  the  kidney-cells  ;  the  material 
is  eliminated  into  the  tubules  as  quickly  as  it  is  received  from  the  blood. 
The  rate  of  elimination  increases  normally  with  the  increase  in  the  urea  in 
the  blood,  as  would  be  expected  upon  the  assumption  that  the  urea  itself  acts 
as  the  physiological  stimulus  to  the  epithelial  cells. 

The  Blood-flow  through  the  Kidneys. — It  will  be  seen  from  the  dis- 
cussion above  that,  other  conditions  remaining  the  same,  the  secretion  of  the 
kidney  varies  with  the  quantity  of  blood  flowing  through  it.  It  is  therefore 
important  at  this  point  to  refer  briefly  to  the  nature  and  especially  the  regula- 
tion of  the  blood-flow  through  this  organ,  although  the  same  subject  is  referred 
to  in  connection  with  the  general  description  of  vaso-motor  regulation  (see 
Circulation).  It  has  been  shown  by  Landergren1  and  Tiegerstedt  that  the 
kidney  is  a  very  vascular  organ,  at  least  when  it  is  in  strong  functional  activ- 
ity such  as  may  be  produced  by  the  action  of  diuretics.  They  estimate  that 
in  a  minute's  time,  under  the  action  of  diuretics,  an  amount  of  blond  flows 
through  the  kidney  equal  to  the  weight  of  the  organ;  this  is  an  amount  from 
four  to  nineteen  times  as  great  as  occurs  in  the  average  supply  of  the  other 
organs  in  the  systemic  circulation.  Taking  both  kidneys  into  account,  their 
figures  show  that  (in  strong  diuresis)  5.6  per  ceut.  of  the  total  quantity  of 
blood  sent  out  of  the  left  heart  in  a  minute  may  pass  through  the  kidneys, 
although  the  combined  weight  of  these  organs  makes  only  0.56  per  cent,  of 
that  of  the  body. 

The  nature  of  the  supply  of  vaso-motor  nerves  to  the  kidney  and  the  con- 
ditions which  bring  then)  into  activity  are  fairly  well  known,  owing  to  the  use- 
ful invention  of  the  oncometer  by  Roy.2  This  instrument  is  in  principle  a 
plethysmograph  especially  modified  for  use  upon  the  kidney  of  the  living 
animal.  It  is  a  kidney-shaped  box  of  thin  brass  made  in  two  parts,  biuged  at 
the  back,  and  with  a  clasp  in  front  to  hold  them  together.  In  the  interior  of 
the  box  thin  peritoneal  membrane  is  so  fastened  to  each  half  that  a  layer  of  olive 
oil  may  be  placed  between  it  ami  the  brass  walls.  There  is  thus  formed  in 
each  half  a  soft  pad  of  oil  upon  which  the  kidney  rests.  When  the  kidney. 
freed  as  far  as  possible  from  fat  and  surrounding  connective  tissue,  but  with 
the  blood-vessels  and  nerves  entering  at  the  hilus  entirely  uninjured,  is  laid  in 

1  Skamdinavisekes  Arehvufiir  Physiologie,  1892,  Bd.  iv.  8.  241. 

2  See  Cohnheim  and  Roy:  Virchou/s  Arehiv,  1883,  Bd.  scii.  S.  -1-4. 


256  AN  AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

one-half  of  the  oncometer,  and  the  other  half  is  shut  down  upon  it  and  tightly 
fastened,  the  organ  is  .surrounded  by  oil  in  a  box  which  is  liquid-tight  at  every 
point  except  one,  where  a  tube  is  led  off  to  some  suitable  recorder  such  as  a 
tambour.  Under  these  conditions  every  increase  in  the  volume  of  the  kidney 
will  cause  a  proportional  outflow  of  oil  from  the  oncometer,  which  will  be 
measured  by  the  recorder,  and  every  diminution  in  volume  will  be  accompa- 
nied by  a  reverse  change.  At  the  same  time  the  flow  of  urine  during  these 
changes  can  be  determined  by  inserting  a  cannula  into  the  ureter  and  measur- 
ing directly  the  outflow  of  urine.  By  this  and  other  means  it  has  been  shown 
that  the  kidney  receives  a  rich  supply  of  vaso-constrictor  nerve-fibres  that 
reach  it  between  and  round  the  entering  blood-vessels.  These  fibres  emerge 
from  the  spinal  cord  chiefly  in  the  lower  thoracic  spinal  nerves  (tenth  to  thir- 
teenth in  the  dog),  pass  through  the  sympathetic  system,  and  reach  the  organ 
as  non-medu Hated  fibres.  Stimulation  of  these  nerves  causes  a  contraction  of 
the  small  arteries  of  the  kidney,  a  shrinkage  in  volume  of  the  whole  organ  as 
measured  by  the  oncometer,  and  a  diminished  secretion  of  urine.  When,  on 
the  other  hand,  these  constrictor  fibres  are  cut  as  they  enter  the  hilus  of  the 
kidney,  the  arteries  are  dilated  on  account  of  the  removal  of  the  tonic  action 
of  the  constrictor  fibres,  the  organ  enlarges,  and  a  greater  quantity  of  blood 
passes  through  it,  since  the  resistance  to  the  blood-flow  is  diminished  while 
the  general  arterial  pressure  in  the  aorta  remains  practically  the  same.  Along 
with  this  greater  flow  of  blood  there  is  a  marked  increase  in  the  secretion  of  urine. 
Under  normal  conditions  we  must  suppose  that  these  fibres  are  brought 
into  play  to  a  greater  or  less  extent  by  reflex  stimulation,  and  thus  serve  to 
control  the  blood-flow  through  the  kidney  and  thereby  influence  its  functional 
activity.  It  has  been  shown,  too,  that  the  kidney  receives  vaso-dilator  nerve- 
fibres,  that  is,  fibres  which  when  stimulated  directly  or  reflexly  cause  a  dilata- 
tion of  the  arteries,  and  therefore  a  greater  flow  of  blood  through  the  organ. 
According  to  Bradford,1  these  fibres  emerge  from  the  spinal  cord  mainly  in  the 
anterior  roots  of  the  eleventh,  twelfth,  and  thirteenth  spinal  nerves.  Under 
normal  conditions  these  fibres  are  probably  thrown  into  action  by  reflex  stimula- 
tion and  lead  to  an  increased  functional  activity.  It  will  be  seen,  therefore, 
that  the  kidneys  possess  a  local  nervous  mechanism  through  which  their 
secretory  activity  may  be  increased  or  diminished  by  corresponding  alterations 
in  the  blood-supply.  So  far  as  is  known,  this  is  the  only  way  in  which  the 
secretion  in  the  kidneys  can  be  directly  affected  by  the  central  nervous  system. 
It  should  be  borne  in  mind,  also,  that  the  blood-flow  through  the  kidneys, 
and  therefore  their  secretory  activity,  may  be  affected  by  conditions  influ- 
encing general  arterial  pressure.  Conditions  such  as  asphyxia,  strychnin- 
poisoning,  or  painful  stimulation  of  sensorv  nerves,  which  cause  a  general 
vaso- constriction,  influence  the  kidney  in  the  same  way,  and  tend,  therefore, 
to  diminish  the  flow  of  blood  through  it;  while  conditions  which  lower 
general   arterial    pressure,  such  as  general   vascular  dilatation  of  the  skin 

1  Journal  of  Physiology,  1889,  vol.  x.  p.  358. 


SECRETION.  257 

vessels,  may  also  depress  the  secretory  action  of  the  kidney  by  diminishing 
the  amount  of  blood  flowing  through  it. 

In  what  way  any  given  change  in  the  vascular  conditions  of  the  body  will 
influence  the  secretion  of  the  kidney  depends  upon  a  number  of  factors,  and 
their  relations  to  one  another  ;  but  any  change  which  will  increase  the  differ- 
ence in  pressure  between  the  blood  in  the  renal  artery  and  the  renal  vein  will 
tend  to  augment  the  flow  of  blood  unless  it  is  antagonized  by  a  simultaneous 
constriction  in  the  small  arteries  of  the  kidney  itself.  On  the  contrary,  any 
vascular  dilatation  of  the  vessels  in  the  kiduey  will  tend  to  increase  the  blood- 
flow  through  it  unless  there  is  at  the  same  time  such  a  general  fall  of  blood- 
pressure  as  is  sufficient  to  lower  the  pressure  in  the  renal  artery  and  reduce  the 
driving  force  of  the  blood  to  an  extent  that  more  than  counteracts  the  favora- 
ble influence  of  diminished  resistance  in  the  small  arteries. 

Movements  of  the  Ureter  and  the  Bladder. — (See  Micturition,  p.  389.) 

E.  Cutaneous  Glands  ;  Internal  Secretions. 

The  sebaceous  glands,  sweat-glands,  and  mammary  glands  are  all  true  epider- 
mal structures,  and  may  therefore  be  conveniently  treated  together. 

Sebaceous  Secretion. — The  sebaceous  glands  are  simple  or  compound 
alveolar  glands  found  over  the  cutaneous  surface  usually  in  association  with  the 
hairs,  although  in  some  cases  they  occur  separately,  as,  for  instance,  on  the  pre- 
puce and  glans  penis,  and  on  the  lips.  When  they  occur  with  the  hairs  the 
short  duet  opens  into  the  hair-follicle,  so  that  the  secretion  is  passed  out  upon 
the  hair  near  the  point  where  it  projects  from  the  skin.  The  alveoli  are  filled 
with  cuboidal  or  polygonal  epithelial  cells,  which  are  arranged  in  several  lay- 
ers. Those  nearest  the  lumen  of  the  gland  are  filled  with  fatty  material. 
These  cells  are  supposed  to  be  cast  off  bodily,  their  detritus  going  to  form  the 
secretion.  New  cells  are  formed  from  the  layer  nearest  the  basement  mem- 
brane, and  thus  the  glands  continue  to  produce  a  slow  but  continuous  secretion. 
The  sebaceous  secretion,  or  sebum,  is  an  oily  semi-liquid  material  that  sets 
upon  exposure  to  the  air  to  a  cheesy  mass,  as  is  seen  in  the  comedones  or  pim- 
ples which  so  frequently  occur  upon  the  skin  from  occlusion  of  the  opening  of 
the  ducts.  The  exact  composition  of  the  secretion  is  not  known.  It  contains 
fats  and  soaps,  some  cholesterin,  albuminous  material,  pari  of  which  is  a 
nucleo-albumin  often  described  as  a  casein,  remnants  of  epithelial  cells. 
and  inorganic  salts.  The  cholesterin  occurs  in  combination  with  a  fatty  acid 
and  is  found  in  especially  large  quantities  in  sheep's  wool,  from  which  it  is 
extracted  and  used  commercially  under  the  name  of  lanolin.  'The  sebaceous 
secretion  from  different  places,  or  in  different  animals,  is  probably  somewhal 
variable  in  composition  as  well  as  in  quantity.  The  secretion  of  the  prepuce 
is  known  as  the  smegma  prcepvMi;  that  of  the  external  auditory  meatus, 
mixed  with  the  secretion  of  the  neighboring  sweat-glands  or  ceruminous  glands, 
forms  the  well-known  ear-wax  or  cerumen.  The  secretion  in  this  place  con- 
tains a  reddish  pigment  of  a  bitterish-sweet  taste,  the  composition  of  which  has 
not  been  investigated.      Upon   the  skin  of  the  newly-born   the  sel»a< us  ma- 

Vol.  I.— 17 


258  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

terial  is  accumulated  to  form  the  remix  caseosa.  The  well-known  u  ropy  gal 
gland  of  birds  is  homologous  with  the  mammalian  sebaceous  glands,  and  its 
secretion  lias  been  obtained  in  sufficient  quantities  for  chemical  analysis. 
Physiologically  it  is  believed  that  the  .sebaceous  secretion  affords  a  protection 
to  the  skin  and  hairs.  Its  oily  character  doubtless  serves  to  protect  the  hairs 
from  becoming  too  brittle,  or,  on  the  other  hand,  from  being  too  easily  satu- 
rated with  external  moisture.  In  this  way  it  probably  aids  in  making  the 
hairy  coat  a  more  perfect  protection  against  the  effect  of  external  changes  of 
temperature.  Upon  the  surface  of  the  skin  also  it  forms  a  thin  protective 
layer  that  tends  to  prevent  undue  loss  of  heat  from  evaporation,  and  possi- 
bly is  important  in  other  ways  in  maintaining  the  physiological  integrity  of 
the  external  surface. 

Sweat. — The  sweat  or  perspiration  is  a  secretion  of  the  sweat-glands. 
These  latter  structures  are  found  over  the  entire  cutaneous  surface  except  in 
the  deeper  portions  of  the  external  auditory  meatus.  They  are  particularly 
abundant  upon  the  palms  of  the  hands  and  the  soles  of  the  feet.  Krause 
estimates  that  their  total  number  for  the  whole  cutaneous  surface  is  about  two 
millions.  In  man  they  are  formed  on  the  type  of  simple  tubular  glands,  the 
terminal  portion  contains  the  secretory  cells,  and  at  this  part  the  tube  is 
usually  coiled  to  make  a  more  or  less  compact  knot,  thus  increasing  the  extent 
of  the  secreting  surface.  The  larger  ducts  have  a  thin  muscular  coat  of  invol- 
untary  tissue  that  may  possibly  be  concerned  in  the  ejection  of  the  secretion. 
The  secretory  cells  in  the  terminal  portion  are  columnar  in  shape,  they  possess 
a  granular  cytoplasm  and  are  arranged  in  a  single  layer.  The  amount  of 
secretion  formed  by  these  glands  varies  greatly,  being  influenced  by  the  con- 
dition of  the  atmosphere  as  regards  temperature  and  moisture,  as  well  as  by 
various  physical  and  psychical  states,  such  as  exercise  and  emotions.  The 
average  quantity  for  twenty-four  hours  is  said  to  vary  between  TOO  and  900 
grams,  although  this  amount  may  be  doubled  under  certain  conditions. 

According  to  an  interesting  paper  by  Schierbeck,1  the  average  quantity 
of  sweat  in  twenty-four  hours  may  amount  to  2  to  3  liters  in  a  person  clothed, 
and  therefore  with  an  average  temperature  of  32°  C.  surrounding  the  skin. 
This  author  states  that  the  amount  of  sweat  given  off  from  the  skin  in  the 
form  of  insensible  perspiration  increases  proportionately  with  the  tempera- 
ture until  a  certain  critical  point  is  reached  (about  33°  C.  in  the  person 
investigated),  when  there  is  a  marked  increase  in  the  water  eliminated,  the 
increase  being  simultaneous  with  the  formation  of  visible  sweat.  At  the  same 
time  there  is  a  more  marked  and  sudden  increase  in  the  CO.,  eliminated  from 
the  skin,  from  8  grams  to  20  grams  in  twenty-four  hours.  It  is  possible  that 
the  sudden  increase  in  (X ).,  is  an  indication  of  greater  metabolism  in  the  sweat- 
glands  in  connection  with  the  formation  of  visible  sweat. 

Composition  oftht  Secretion. — The  precise  chemical  composition  of  sweat 
is  difficull  to  determine,  owing  to  the  fact  that  as  usually  obtained  it  is  liable 
1  Archivfur  Anatomieund  Physiologie  (Physiol.  Abtheil),  1893,  S.  llfi. 


SECRETION.  259 

to  be  mixed  with  the  sebaceous  secretion.  Normally  it  is  a  very  thin  secre- 
tion of  low  specific  gravity  (1004)  and  an  alkaline  reaction,  although  when 
first  secreted  the  reaction  may  be  acid  owing  to  admixture  with  the  sebaceous 
material.  The  larger  part  of  the  inorganic  salts  consists  of  sodium  chloride. 
Small  quantities  of  the  alkaline  sulphates  and  phosphates  arc  also  present.  The 
organic  constituents,  though  present  in  mere  traces,  are  quite  varied  in  num- 
ber. Urea,  uric  acid,  creatinin,  aromatic  oxy-  acids,  ethereal  sulphates  of 
phenol  and  skatol,  and  albumin,  are  said  to  occur  when  the  sweating  is  pro- 
fuse. Argutinsky  has  shown  that  after  the  action  of  vapor-baths,  and  as  the 
result  of  muscular  work,  the  amount  of  urea  eliminated  in  this  secretion  may 
be  considerable  (see  p.  360).  Under  pathological  conditions  involving  a 
diminished  elimination  of  urea  through  the  kidneys  it  has  been  observed  that 
the  amount  found  in  the  sweat  is  markedly  increased,  so  that  crystals  of  it 
may  be  deposited  upon  the  skin.  Under  perfectly  normal  conditions,  how- 
ever, it  is  obvious  that  the  organic  constituents  are  of  minor  importance.  The 
main  fact  to  be  considered  in  the  secretion  of  sweat  is  the  formation  of  water. 
Secretory  Fibres  to  the  Sweat-glands. — Definite  experimental  proof  of  the 
existence  of  sweat-nerves  was  first  obtained  by  Goltz  l  in  some  experiments 
upou  stimulation  of  the  sciatic  nerve  in  cats.  In  the  cat  and  dog,  in  which 
sweat-glands  occur  on  the  balls  of  the  feet,  the  presence  of  sweat-nerves  may 
be  demonstrated  with  great  ease.  Electrical  stimulation  of  the  peripheral 
end  of  the  divided  sciatic  nerve,  if  sufficiently  strong,  will  cause  visible  drops 
of  sweat  to  form  on  the  hairless  skin  of  the  balls  of  the  feet.  When  the  elec- 
trodes are  kept  at  the  same  spot  on  the  nerve  and  the  stimulation  is  maintained 
the  secretion  soon  ceases,  but  this  effect  seems  to  be  due  to  a  temporary  injury 
of  some  kind  to  the  nerve-fibres  at  the  point  of  stimulation,  and  not  to  a 
genuiue  fatigue  of  the  sweat-glands  or  the  sweat-fibres,  since  moving  the  elec- 
trodes to  a  new  point  on  the  nerve  farther  toward  the  periphery  calls  forth  a 
new  secretion.  The  secretion  so  formed  is  thin  and  limpid,  and  has  a  marked 
alkaline  reaction.  The  anatomical  course  of  these  fibres  has  been  worked  out 
in  the  cat  with  great  care  by  Langley.2  He  finds  that  for  the  hind  feet  they 
leave  the  spinal  cord  chiefly  in  the  first  and  second  lumbar  nerves,  enter  the 
sympathetic  chain,  and  emerge  from  this  as  non-medullated  fibres  in  the  gray 
rami  proceeding  from  the  sixth  lumbar  to  the  second  sacral  ganglion,  but 
chiefly  in  the  seventh  lumbar  and  first  sacral,  and  then  join  the  nerves  of 
the  sciatic  plexus.  For  the  fore  feet  the  fibres  leave  the  spinal  cord  in  the 
fourth  to  the  tenth  thoracic  nerves,  enter  the  sympathetic  chain,  pass  upward 
to  the  first  thoracic  ganglion,  whence  they  are  continued  as  non-medullated 
fibres  thai  pass  out  of  this  ganglion  by  the  gray  rami  communicating  with 
the  nerves  forming  the  brachial  plexus.  The  action  of  the  nerve-fibres  upon 
the  sweat-glands  cannot  be  explained  as  an  indirect  effect  —  for  instance,  as  a 
result  of  a  variation  in  the  blood-flow.  Experiments  have  repeatedly  shown 
that,  in  the  cat,  stimulation  of  the  sciatic  still  calls  forth  a  secretion  after  the 

1  Archiv  fur  die  gesammte  Physiologic,  1875,  Bd.  \i.  B.  71. 

2  Journal  of  Physiology,  1891,  vol.  xii.  p.  347. 


260  AN  AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

blood  has  been  shut  off  from  the  leg  by  ligation  of  the  aorta,  or  indeed  after 
the  leg  has  beeu  amputated  for  as  long  as  twenty  minutes.  So  in  human 
beings  it  is  known  that  profuse  sweating  may  often  accompany  a  pallid  skin, 
as  in  terror  or  nausea,  while  on  the  other  hand  the  Hushed  skin  of  fever  is 
characterized  by  the  absence  of  perspiration.  There  seems  to  be  no  doubt 
at  all  that  the  sweat-nerve-  are  genuine  secretory  fibres,  causing  a  secretion 
in  consequence  of  a  direct  action  on  the  cells  of  the  sweat-glands.  In  accord- 
ance with  this  physiological  fact  histological  work  has  demonstrated  that 
special  nerve-fibres  are  supplied  to  the  glandular  epithelium.  According  to 
Arnstein  '  the  terminal  fibres  form  a  small  branching  varicose  ending  in  con- 
tact with  the  epithelial  cells.  The  sweat-gland  may  be  made  to  secrete  in 
many  ways  other  than  by  direct  artificial  excitation  of  the  sweat-fibres;  for 
example,  by  external  heat,  dyspnoea,  muscular  exercise,  strong  emotions,  and 
by  the  action  of  various  drugs  such  as  pilocarpin,  muscarin,  strychnin,  nicotin, 
picrotoxin,  and  physostigmin.  In  all  such  cases  the  effect  is  supposed  to 
result  from  an  action  on  the  sweat-fibres,  either  directly  on  their  terminations, 
or  indirectly  upon  their  cells  of  origin  in  the  central  nervous  system.  In 
ordinary  life  the  usual  cause  of  profuse  sweating  is  a  high  external  temper- 
ature or  muscular  exercise.  With  regard  to  the  former  it  is  known  that 
the  high  temperature  does  not  excite  the  sweat-glands  immediately,  but 
through  the  intervention  of  the  central  nervous  system.  If  the  nerves  going 
to  a  limb  be  cut,  exposure  of  that  limb  to  a  high  temperature  does  not  cause 
a  secretion,  showing  that  the  temperature  change  aloue  is  not  sufficient  to 
excite  the  gland  or  its  terminal  nerve-fibres.  AVe  must  suppose,  therefore, 
that  the  high  temperature  acts  upon  the  sensory  cutaneous  nerves,  possibly 
the  heat-fibres,  and  reflexly  stimulates  the  sweat-fibres.  Although  external 
temperature  does  not  directly  excite  the  glands,  it  should  be  stated  that  it 
affects  their  irritability  either  by  direct  action  on  the  gland-cells  or  upon  the 
terminal  nerve-fibres.  At  a  sufficiently  low  temperature  the  cat's  paw  does 
not  secrete  at  all,  and  the  irritability  of  the  glands  is  increased  by  a  rise  of 
temperature  up  to  about  45°  C. 

Dyspnoea,  muscular  exercise,  emotions,  and  many  drugs  affect  the  secretion, 
probably  by  action  on  the  nerve-centres.  Pilocarpin,  on  the  contrary,  is 
known  to  stimulate  the  endings  of  the  nerve-fibres  in  the  glands,  while  atropin 
has  the  opposite  effect,  completely  paralyzing  the  secretory  fibres. 

Sweat-centres  in  the  Central  Nervous  System. — The  fact  that  secretion  of 
sweat  may  be  occasioned  by  stimulation  of  afferent  nerves  or  by  direct  action 
upon  the  central  nervous  system,  as  in  the  case  of  dyspnoea,  implies  the  exi-t- 
ence  of  physiological  centres  controlling  the  secretory  fibres.  The  precise  loca- 
tion of  the  sweat-centre  or  centres  has  not,  however,  been  satisfactorily  deter- 
mined. Histologically  and  anatomically  the  arrangement  of  the  sweat-fibres 
resembles  that  of  the  vaso-constrictor  fibres,  and,  reasoning  from  analogy,  one 
might  suppose  the  existence  of  a  general  sweat-centre  in  the  medulla  compara- 
ble to  the  vaso-constrictor  centre,  but  positive  evidence  of  the  existence  of  such 
1  Anatomischer  Anzcujer,  1895,  Bd.  x. 


SECRETION.  261 

an  arrangement  is  lacking.  It  has  been  shown  than  when  the  medulla  is 
separated  from  the  cord  by  a  section  in  the  cervical  or  thoracic  region  the 
action  of  dyspnoea,  or  of  various  sudorific  drugs  supposed  to  act  on  the  cen- 
tral nervous  system,  may  still  cause  a  secretion.  On  the  evidence  of  results 
of  this  character  it  is  assumed  that  there  are  spinal  sweat-centres,  but  whether 
these  are  few  in  number  or  represent  simply  the  various  nuclei  of  origin  of  the 
fibres  to  different  regions  is  not  definitely  known.  It  is  possible  that  in  addi- 
tion to  these  spinal  centres  there  is  a  general  regulating  centre  in  the  medulla. 

Mammary  Glands. 

The  mammary  glands  are  undoubtedly  epidermal  structures  comparable  in 
development  to  the  sweat-  or  the  sebaceous  glands.  Whether  they  are  to  be 
homologized  with  the  sweat-  or  with  the  sebaceous  glands  is  not  clearly  deter- 
mined. In  most  animals  they  are  compound  alveolar  glands,  and  their  acinous 
structure  and  the  rich  albuminous  and  fatty  constituents  of  their  secretion 
would  seem  to  suggest  a  relationship  to  the  sebaceous  glands.  But  the  histo- 
logical structure  of  the  alveolus  with  its  single  layer  of  epithelium  points 
rather  to  a  connection  with  the  sweat-glands.  Whatever  may  have  been  their 
exact  origin  in  the  primitive  mammalia,  there  seems  to  be  no  question  that 
they  were  derived  in  the  first  place  from  some  of  the  ordinary  skin-glands 
which  at  first  simply  opened,  without  a  distinct  mamma  or  nipple,  on  a  defi- 
nite area  of  the  skin,  as  is  seen  now  in  the  case  of  the  monotremes.  Later 
in  the  phylogenetic  history  of  the  gland  the  separate  ducts  united  to  form 
one  or  more  larger  ones,  and  these  opened  to  the  exterior  upon  the  protrusion 
of  the  skin  known  as  the  nipple.  The  number  and  position  of  the  glands 
vary  much  in  the  different  mammalia.  In  man  they  are  found  in  the  thoracic 
region  and  are  normally  two  in  number.  The  milk-ducts  do  not  unite  to 
form  a  single  canal,  but  form  a  group  of  fifteen  to  twenty  separate  systems, 
each  of  which  opens  separately  upon  the  surface  of  the  nipple.  Before  preg- 
nancy the  secreting  alveoli  are  incompletely  formed,  but  during  pregnancy 
and  at  the  time  lactation  begins  the  formation  of  the  alveoli  is  greatly  acceler- 
ated by  proliferation  of  the  epithelial  cells. 

Composition  of  the  Secretion. — The  general  appearance  and  composi- 
tion of  the  milk  are  well  known.  Microscopically  milk  consists  of  a  liquid 
portion,  or  plasma,  in  which  float  an  innumerable  multitude  of  fine  fat-drop- 
lets. The  latter  elements  contain  the  milk-fat,  which  consists  chiefly  of  neutral 
fats,  stearin,  palmitin,  and  olein,  but  contains  also  a  small  amount  of  the  fata 
of  butyric  and  caproic  acid  as  well  as  slight  traces  of  other  fatty  acid  emu- 
pounds  and  small  amounts  of  lecithin,  cholesterin,  and  a  yellow  pigment.  Upon 
standing,  a  portion  of  these  elements  rises  to  the  surface  to  form  the  cream.  The 
milk-plasma  holds  in  solution  important  proteid  and  carbohydrate  compounds 
as  well  as  the  necessary  inorganic  salts.  The  proteids  are  casein,  belonging  to 
the  group  of  nucleo-albumins  ;  lactalbumin,  which  closely  resembles  thesenun- 
albumin  of  blood,  and  lacto-globulin,  which  is  similar  to  the  paraglobulin  of 
blood  :  the  two  latter  proteids  occur  in  much  smaller  quantities  than  the  casein. 


262 


AN  AMERICA X    TEXT-BOOK    OF  PHYSIOLOGY. 


The  chief  rail )« >liydrate  in  milk  is  the  milk-sugar  or  lactose.  Hammarsten  x 
has  succeeded  in  isolating  from  the  mammary  gland  a  nucleo-proteid  contain- 
ing a  reducing  group.  He  designates  this  substance  as  nucleo-glyco-proteid. 
It  -cciiis  possible  that  a  compound  of  this  character  might  serve  as  the  parent 
substance  for  both  the  casein  and  the  lactose  of  the  secretion.  The  mineral 
constituents  are  varied  and,  considered  quantitatively,  show  an  interesting  rela- 
tionship to  the  mineral  composition  of  the  body  of  the  suckling  (see  p.  867). 
The  fact  that  the  inorganic  salts  of  the  milk  vary  so  widely  in  quantitative 
composition  from  those  of  the  blood  has  been  used  to  show  that  they  are  not 
derived  from  the  blood  by  the  simple  mechanical  processes  of  filtration  and 
diffusion,  but  are  secreted  by  the  epithelial  cells  of  the  glands.  Traces  of 
nitrogeneous  excreta,  such  as  urea,  creatin,  and  creatinin,  are  also  found  in 
tin  milk-plasma,  together  with  some  lecithin  and  cholesterin  and  a  small 
amount   of  citric  acid  occurring  as  citrate  of  calcium. 

Histological  Changes  during  Secretion. — The  simple  fact  that  sub- 
stances are  found  in  the  milk  which  do  not  occur  in  the  blood  or  lymph  is 
sufficient  proof  that  the  epithelial  cells  are  actively  concerned  in  the  process 
of  secretion.     Histological  examination  of  the  gland  during  lactation  confirms 

fully  this  a  'priori  deduction,  and  enables 
us  to  understand  the  probable  origin  of 
some  of  the  important  constituents.2  In 
the  resting  gland  during  the  period  of 
gestation,  or  in  certain  alveoli  during 
lactation,  the  alveoli  are  lined  by  a  single 
layer  of  flattened  or  cuboidal  cells,  which 
have  only  a  single  nucleus,  present  a 
granular  appearance,  and  have  few  or 
no  fat-globules  in  them  (Fig.  QQ). 
When  such  alveoli  enter  into  the  active 
formation  of  milk  the  epithelial  cells 
increase  in  height,  projecting  in  toward  the  lumen,  the  nuclei  divide,  and  as  a 


Fig.  66.— Suction  through  the  middle  of  two 
alveoli  of  the  mammary  gland  of  the  dog;  con- 
dition of  re.^t  i alter  Ileidenhain). 


A  B 

Fig.  67.— Mammary  gland  of  dog,  showing  the  formation  of  the  secretion:  A,  medium  condition  of 
gn  fwth  of  the  epithelial  cells ;  B,  a  later  condition  (after  Heidenhain). 

rule  (Steinhaus3)  each  cell  contains  two  nuclei  (Fig.  67).      Fat-droplets  de- 
velop in  the  cytoplasm,  especially  in  the  free  end  of  the  cell,  and  according  to 

1  Zeitechrift  fur  physiologisehe  Cltemie,  1894,  Bd.  xix.  S.  19. 

2  See  Heidenhain:  Hermann's  Handbuch  der  Physiologie,  1883,  Bd.  v.  S.  381. 

3  Du  Bois-Reymond's  Arehiv  fur  Physiologic,  1892,  Suppl.  I'>d.,  8.  54. 


SECRETION.  263 

Steinhaus  the  nucleus  nearest  the  lumen  undergoes  a  fattv  metamorphosis. 
According  to  the  same  author  the  granular  material  in  the  cytoplasm  also 
undergoes  a  visible  change;  the  granules,  which  in  the  resting  cell  are 
spherical,  elongate  during  the  stage  of  activity  to  threads  thai  take  on  a 
spirochaeta-like  form.  The  acme  of  this  phase  of  development  is  reached  by 
the  solution  or  disintegration  of  a  portion  of  the  end  of  the  cell,  the  frag- 
ments being  discharged  into  the  lumen  of  the  alveolus.  The  debris  of  this 
disintegrated  portion  of  the  cell  helps  to  form  the  secretion  ;  part  of  it  goes 
into  solution  to  form,  probably,  the  albuminous  and  carbohydrate  constituents, 
while  the  fat-droplets  are  set  free  to  form  the  milk-fat.  Apparently  the  basal 
portion  of  the  cell  regenerates  its  cytoplasm  and  thus  continues  to  form  oew 
material  for  the  secretion.  In  some  cases,  however,  the  whole  cell  seems  to 
undergo  dissolution,  and  its  place  is  taken  by  a  new  cell  formed  by  karvo- 
kinetic  division  of  one  of  the  neighboring  epithelial  cells.  The  origin  of  the 
peculiar  colostrum  corpuscles  found  in  the  milk  during  the  first  few  days 
of  its  secretion  has  been  explained  differently  by  different  observers.  Heid- 
enhain  traces  them  to  certain  epithelial  cells  of  the  alveoli  which  at  this 
time  become  rounded,  develop  numerous  fat-droplets,  and  are  finally  dis- 
charged bodily  into  the  lumen,  although  he  was  not  able  to  actually  trace 
the  intermediate  steps  in  the  process.  Steinhaus,  on  the  contrary,  thinks 
that  these  corpuscles  are  derived  from  the  wandering  cells  of  the  connective 
tissue  (Mastzellen)  which  at  the  beginning  of  lactation  are  very  numerous, 
but  seem  to  undergo  fatty  degeneration  and  elimination  in  the  secretion  of 
the  newly  active  gland. 

Control  of  the  Secretion  by  the  Nervous  System. — There  are  indica- 
tions that  the  secretion  of  the  mammary  glands  is  under  the  control,  to  some 
extent  at  least,  of  the  central  nervous  system.  For  instance,  in  women  during 
the  period  of  lactation  cases  have  been  recorded  in  which  the  secretion  was 
altered  or  perhaps  entirely  suppressed  by  strong  emotions, by  an  epileptic  attack, 
etc.  This  indication  has  not  received  satisfactory  confirmation  from  the  side 
of  experimental  physiology.  Eckhard1  found  that  section  of  the  main  nerve- 
trunk  supplying  the  gland  in  goats,  the  external  spermatic,  caused  no  dif- 
ference in  the  quantity  or  quality  of  the  secretion.  Rohrig2  obtained  more 
positive  results,  inasmuch  as  he  found  that  some  of  the  branches  of  the  exter- 
nal spermatic  supply  vaso-motor  fibres  to  the  blood-vessels  of  the  gland  and 
influence  the  secretion  of  milk  by  controlling  the  local  blood-How  in  the 
gland.  Section  of  the  inferior  branch  of  this  nerve,  for  example,  gave  in- 
creased secretion,  while  stimulation  caused  diminished  secretion,  as  in  the 
case  of  the  vaso-constrictor  fibres  to  the  kidney.  These  results  have  qoI  been 
confirmed  by  others — in  fact,  they  have  been  subjected  to  adverse  criticism — 
and  they  cannot,  therefore,  be  accepted  unhesitatingly. 

Mironow 1  reports  a  Dumber  of  interesting  experiments  made  upon  goats. 

1  See  Heidenhain :   Hermawnfs  Handbuch  der  Physiologic,  Bd.  v.  Thl.  1.  8.  392. 

2  Virr/imi-'s  Archir  fur  pathologiache  Anatomie,  etc.,  1876,  Bd.  67,  8.  119. 

3  Archives  <lrx  Science*  hiii/iii/it/iics,  St.  Petersburg,  IS'.M,  t.  iii.  p.  :'.',.",. 


2(34  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

He  found  that  artificial  stimulation  of  sensory  nerves  causes  a  diminution  in 
the  amount  of  secretion,  thus  confirming  the  opinion  based  upon  observations 
upon  the  human  being,  that  in  some  way  the  central  nervous  system  exerts  an 
influence  on  the  mammary  gland.  When  the  mammary  glands  are  com- 
pletely isolated  from  their  connections  with  the  central  nervous  system,  stimu- 
lation of  an  afferent  nerve  no  longer  influences  the  secretion.  Mironow 
states  also  that  although  section  of  the  external  spermatic  on  one  side  does  not 
influence  the  secretion,  section  of  this  nerve  on  both  sides  is  followed  by  a 
marked  diminution,  and  the  same  result  is  obtained  when  the  gland  on  one 
side  is  completely  isolated  from  all  nervous  connections.  The  diminution  of 
the  secretion  in  these  cases  comes  on  very  slowly,  after  a  number  of  days,  so 
that  the  effect  cannot  be  attributed  to  the  removal  of  definite  secretory  fibres. 
Moreover,  after  apparently  complete  separation  of  the  gland  from  all  its 
extrinsic  nerves,  not  only  does  the  secretion,  if  it  was  previously  present,  con- 
tinue to  form  although  in  less  quantities,  but  in  operations  of  this  kind  upon 
pregnant  animals  the  glands  increase  in  size  during  pregnancy  and  become 
functional  after  the  act  of  parturition. 

Experiments,  therefore,  as  far  as  they  have  been  carried,  indicate  that 
the  gland  is  under  the  regulating  control  of  the  central  nervous  system,  either 
through  secretory  or  vaso-motor  fibres,  but  that  it  is  essentially  an  automatic 
organ.  The  bond  of  connection  between  it  and  the  uterus  seems  to  be,  in  part 
if  not  entirely,  through  the  blood  rather  than  through  the  nervous  system. 
It  should  be  added  that  Arnstein  1  has  described  a  definite  connection  between 
the  nerve-fibres  and  the  epithelial  cells  of  the  gland.  If  this  fact  is  corrobo- 
rated it  would  amount  to  an  histological  proof  of  the  existence  of  special 
secretory  fibres,  but  the  physiological  evidence  for  the  same  fact  is  either 
negative  or  unsatisfactory. 

Normal  Secretion  of  the  Milk. — As  was  said  in  speaking  of  the  his- 
tology of  the  gland,  the  secreting  alveoli  are  not  fully  formed  until  the  first 
pregnancy.  During  the  period  of  gestation  the  epithelial  cells  multiply,  the 
alveoli  are  formed,  and  after  parturition  secretion  begins.  At  first  the  secre- 
tion  is  not  true  milk,  but  a  liquid  differing  in  composition  and  known  as  the 
colostrum ;  this  secretion  is  characterized  microscopically  by  the  existence  of 
the  colostrum  corpuscles,  which  seem  to  be  wandering  cells  that  have  under- 
gone a  complete  fatty  degeneration.  After  a  few  days  the  true  milk  is  formed 
in  the  manner  already  described.  According  to  Rohrig  the  secretion  is  con- 
tinuous, but  this  statement  needs  confirmation.  As  the  liquid  is  formed  it 
accumulates  in  the  enlarged  galactophoraus  ducts,  and  after  the  tension  has 
reached  a  certain  point  further  secretion  is  apparently  inhibited.  If  the  ducts 
are  emptied,  by  the  infant  or  otherwise,  a  new  secretion  begins.  The  emptying 
of  the  ducts,  in  fact,  seems  to  constitute  the  normal  physiological  stimulus  to 
the  gland-cells,  but  how  this  act  affects  the  secreting  cells,  whether  reflexly  or 
directly,  is  not  known.  When  the  child  is  weaned  the  secretion  under  normal 
conditions  soon  ceases  and  the  alveoli  undergo  retrograde  changes,  although 
1  Anatomischer  Anzeiger,  L895,  Bd.  x.  S.  410. 


SECRETION.  265 

they  do  not  return  completely  to  the  condition  they  were  in  before  the  first 
pregnancy. 

Internal  Secretions. 

According  to  the  definition  proposed  on  p.  211,  the  term  internal  secretion 
is  here  used  to  mean  a  specific  substance  or  substances  formed  within  a  gland- 
ular organ  and  given  off  to  the  blood  or  lymph.  As  was  said  before,  it  is 
difficult  to  make  a  distinction  between  these  internal  secretions  and  the  waste 
products  of  metabolism  generally  so  far  as  method  and  place  of  formation 
and  elimination  are  concerned.  Every  active  tissue  gives  off  waste  products 
that  are  borne  off  in  the  lymph  and  blood,  but  as  generallv  emploved  the 
term  internal  secretion  is  not  meant  to  include  all  such  products,  but  only  the 
materials  produced  in  distinctly  glandular  organs  which  are  more  or  less 
specific  to  those  organs,  and  which  are  supposed  to  have  a  general  value  to 
the  body  as  a  whole.  The  idea  of  an  internal  secretion  seems  to  have  been 
suggested  by  Bernard,  but  was  first  seriously  forced  upon  the  attention  of 
physiologists  by  Brown-Sequard  in  the  course  of  some  work  upon  extracts 
of  the  testis.  Within  the  last  few  years  the  term  has  been  frequently  used, 
especially  in  connection  with  the  valuable  and  interesting  work  done  upon  the 
pancreas  and  the  so-called  blood-vascular  or  ductless  glands,  the  thyroids, 
adrenals,  pituitary  body,  and  spleen.  In  almost  all  cases  our  knowledge  of 
the  nature  and  importance  of  these  internal  secretions  is  in  a  formative  stage ; 
the  literature,  however,  of  the  subject  is  already  very  great,  and  is  increasing 
rapidly,  while  speculations  are  numerous,  so  that  constant  contact  with  current 
literature  is  necessary  to  keep  pace  with  the  advance  in  knowledge. 

Liver. — It  has  not  been  customary  to  speak  of  the  liver  as  furnishing  an 
internal  secretion,  but  two  of  the  products  formed  within  this  organ  are  so 
clearly  known  and  their  method  of  production  is  so  typical  of  what  is  sup- 
posed to  be  the  mechanism  of  internal  secretion,  that  it  is  desirable  both  for 
the  sake  of  convenience  and  consistency  to  include  them  under  this  general 
heading.  Glycogen  (C6H10O5)n  is  formed  within  the  liver-cells  from  the 
sugars  and  proteids  brought  to  them  in  the  blood  of  the  portal  vein,  and  in 
many  cases  the  presence  of  this  glycogen  can  be  demonstrated  microscopically 
within  the  cells.  From  time  to  time,  however,  the  glycogen  within  the  cell 
is  converted  into  dextrose  by  a  process  of  hydration, 

C6H10O6  +  H2O  =  C8H12O65 

and  the  sugar  so  formed  is  by  a  secretory  process  of  some  kind  given  off  to 
the  blood  to  serve  for  the  metabolism  of  the  other  tissues  ..T  the  body,  es- 
pecially the  muscles.  This  elimination  of  its  stored  glycogen  on  the  part  of 
the  liver  may  be  regarded  as  a  case  of  internal  secret  inn.  |  For  further  details 
concerning  glycogen,  its  properties  and  functions,  see  p.  326  and  the  section 
on    Chemistry.)     A  second  substance  which   is    formed   under  the    influence 

of  the  liver-cells  and  is  then  eliminated  into  the  bl 1  is  urea.     Urea  constitutes 

the  chief  nitrogenous  end-product  of  the  metabolism  of  the  proteid  tissues  ;  it 


266  AN    AMERICAN    TEXT- HOOK    OF  PHYSIOLOGY. 

is  eliminated  from  the  body  by  the  kidneys,  but  it  is  known  not  to  be  formed 
in  these  organs.  Modern  investigations  have  seemed  to  show  conclusively 
that  this  substance  is  formed  mainly  within  the  liver  from  some  ante- 
cedent body  (ammonia  compound)  which  arises  in  the  proteid  tissues 
generally,  but  is  not  prepared  for  final  elimination  until  in  the  liver  or  else- 
where it  is  converted  into  urea.  Here  again  the  liver-cells  perform  a  metab- 
olism for  the  good  of  the  organism  as  a  whole,  and  the  act  of  passing  out 
the  urea  into  the  blood  may  be  regarded  as  an  internal  secretion.  It  is  quite 
possible  that  in  still  other  ways  the  liver-cells  add  to  the  blood  elements  of 
importance  to  the  tissues  of  the  body — as,  for  example,  in  the  conservation  and 
distribution  of  the  iron  of  broken-down  haemoglobin  (see  p.  323),  or  in  the  syn- 
thetic combination  of  the  products  of  putrefaction  formed  in  the  intestines  (indol, 
skatol,  phenol,  ete.)  with  sulphuric  acid  (see  p.  340) ;  but  concerning  these  mat- 
ters our  knowledge  is  not  yet  sufficiently  definite  to  make  positive  statements. 
Pancreas. — The  importance  of  the  external  secretion,  the  pancreatic  juice, 
of  the  pancreas  has  long  been  recognized,  but  it  was  not  until  1889  that  von 
Mehring1  and  Minkowski  proved  that  it  furnishes  also  an  equally  important 
internal  secretion.  These  observers  succeeded  in  extirpating  the  entire  pan- 
creas without  causing  the  immediate  death  of  the  animal,  and  found  that  in 
all  eases  this  operation  was  followed  by  the  appearance  of  sugar  in  the  urine 
in  considerable  quantities.  Further  observations  of  their  own  and  other  experi- 
menters '  have  corroborated  this  result  and  added  a  number  of  interesting  facts 
to  our  knowledge  of  this  side  of  the  activity  of  the  pancreas.  It  has  been 
shown  that  when  the  pancreas  is  completely  removed  a  condition  of  glycosuria 
inevitably  follows,  even  if  carbohydrate  food  is  excluded  from  the  diet.  More- 
over, as  in  the  similar  pathological  condition  of  glycosuria  or  diabetes  mellitus 
in  man,  there  is  an  increase  in  the  quantity  of  urine  (polyuria)  and  of  urea, 
and  an  abnormal  thirst  and  hunger.  Acetone  also  is  present  in  the  urine. 
These  symptoms  in  cases  of  complete  extirpation  of  the  pancreas  are  followed 
by  emaciation  and  muscular  weakness,  which  finally  end  in  death  in  two  to 
four  weeks.  If  the  pancreas  is  incompletely  removed,  the  glycosuria  may  be 
serious,  or  slight  and  transient,  or  absent  altogether,  depending  upon  the 
amount  of  pancreatic  tissue  left.  According  to  the  experiments  of  von 
Mehring  and  Minkowski  on  dogs,  a  residue  of  one-fourth  to  one-fifth  of  the 
gland  is  sufficient  to  prevent  the  appearance  of  sugar  in  the  urine,  although 
a  smaller  fragment  may  suffice  apparently  if  its  physiological  condition'  is 
favorable.  The  portion  of  pancreas  left  in  the  body  may  suffice  to  prevent 
glycosuria,  partly  or  completely,  even  though  its  connection  with  the  duo- 
denum is  entirely  interrupted,  thus  indicating  that  the  suppression  of  the 
pancreatic  juice  is  not  responsible  for  the  glycosuria.  The  same  fact  is  shown 
more  conclusively  by  the  following  experiments:  Glycosuria  after  complete 
removal  of  the  pancreas  from  its  normal  connections  may  be  prevented  par- 

1  Archivfur  exper.  Pathologve  and  Pharmakologie,  1  >90,  Bd.  xxvi.  S.  371.      See  also  Minkow- 
ski, Ibid.,  1S93,  Bd.  xxxi.  S.  85,  for  a  more  complete  account. 

'See  IIe\lon  :    Diab&te  pancriatique,  Travaux  de  Physiologie  Universite  de  MontpeUier,  1898. 


SECRETION.  207 

tially  or  completely  by  grafting  a  portion  of  the  pancreas  elsewhere  in  the 
abdominal  cavity  or  even  under  the  skin.  The  duets  of  the  gland  may  be 
completely  occluded  by  ligature  or  by  injection  of  paraffin  without  causing 
a  condition  of  permanent  glycosuria. 

The  condition  of  glycosuria  produced  by  removal  of  the  pancreas  is  desig- 
nated frequently  as  pancreatic  diabetes  and  offers  many  analogies  to  the  similar 
pathological  condition  in  man  known  as  diabetes  mellitus.  The  cause  of  the 
glycosuria  is  obscure.  It  has  been  shown  that  in  severe  cases  sugar  appears 
in  the  urine  even  when  the  animal  is  deprived  of  food,  although  the  quantity 
is  increased  by  feeding  and  especially  by  carbohydrate  food.  Examination 
of  the  blood  shows  that  the  percentage  of  sugar  in  it  is  increased  above  the 
normal,  from  0.15  per  cent,  to  0.3  or  0.5  per  cent.  In  the  liver,  on  the  con- 
trary, the  supply  of  glycogen  disappears.  Carbohydrate  foods  when  fed  cause 
no  deposition  of  glycogen  in  the  liver,  and  apparently  escape  consumption  in 
the  body,  being  eliminated  in  the  urine.  It  is  said,  however,  that  one  form 
of  sugar,  levulose,  offers  an  exception  to  this  general  rule,  since  it  causes  a 
formation  of  liver  glycogen  and  seemingly  is  consumed  in  the  body. 

We  may  believe  from  these  experiments  that  the  pancreas  produces  a 
substance  of  some  kind  that  is  given  off  to  the  blood  or  lymph,  and  is 
either  necessary  for  the  normal  consumption  of  sugar  in  the  body,  or  else,  as 
is  held  by  some,1  normally  restrains  the  output  of  sugar  from  the  liver  and 
other  sugar-producing  tissues  of  the  body.  What  this  material  is  and  how  it 
acts  has  not  yet  been  determined  satisfactorily.  The  most  plausible  theory 
suggested  is  that  the  internal  secretion  produced  contains  a  special  enzyme, 
glycolytic  enzyme  (Lepine),  whose  presence  in  the  blood  is  necessary  for  the 
consumption  of  the  sugar.  Such  an  enzyme  may  be  obtained  from  blood 
(p.  354),  but  it  is  not  proved  whether  it  is  a  normal  constituent  or  whether  it 
is  produced  after  the  blood  is  shed  by  the  disintegration  of  some  of  its  cor- 
puscular elements.  This  theory  therefore  cannot  be  considered  as  more  than 
a  possibility.  It  is  interesting  and  suggestive  to  state  in  this  connection  that 
post-mortem  examination  in  cases  of  diabetes  mellitus  in  the  human  being  has 
shown  that  this  disease  is  associated  in  some  instances  with  obvious  alterations 
in  the  structure  of  the  pancreas. 

The  Thyroid  Body. — The  thyroids  are  glandular  structures  found  in 
all  the  vertebrates.  In  the  mammalia  they  lie  on  either  side  of  the  trachea 
at  its  junction  with  the  larynx.  In  man  they  are  united  across  the  front  oi 
the  trachea  by  a  narrow  band  or  isthmus,  and  hence  are  sometimes  spoken 
of  as  one  structure,  the  thyroid  body.  In  some  of  the  lower  mammals 
(e.  g.  dog)  the  isthmus  is  often  absent,  The  thyroids  in  man  are  small 
bodies  measuring  about  50  millimeters  in  length  by  30  millimeters  in  width  ; 
they  have  a  distinct  glandular  structure  but  possess  no  ducts.  Histological 
examination  shows  that  they  are  composed  of  a  number  of  closed  vesicles  vary- 
ing in  size.  Each  vesicle  is  lined  by  a  single  layer  of  cuboidal  epithelium, 
while  its  interior  is  filled  by  a  homogeneous  glairy  liquid,  tin' colloid  substance 
1  See  Kaufmann:  Archives  de  Physiologie  normah  ft  pathologique,  1895,  p.  210. 


2(38  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

which  is  found  also  in  the  tissue  between  the  vesicles  lying  in  the  lymph- 
spaces.  This  colloid  substance  is  regarded  as  a  secretion  from  the  epithelial 
cells  of  the  vesicles,  and  Biondi,1  Langendorff,2  and  Hurthle3  claim  to  have 
followed  the  development  of  the  secretion  in  the  epithelial  cells  by  micro- 
chemical  reactions.  While  the  interpretation  of  the  microscopical  appearances 
given  by  these  authors  is  not  the  same,  they  agree  in  believing  that  the  colloid 
material  is  formed  within  some  or  all  of  the  epithelial  cells,  and  is  eliminated 
into  the  lumen  with  or  without  a  disintegration  of  the  cell-substance.  More- 
over. Langendorff  and  Biondi  believe  that  the  colloid  material  is  finallv  dis- 
charged  into  the  lymphatics  by  the  rupture  of  the  vesicles.  The  composition 
of  the  colloid  is  incompletely  known. 

Parathyroids. — The  parathyroids  are  small  bodies,  two  on  each  side,  lying 
lateral  or  posterior  to  the  thyroids.  One  of  them  may  be  enclosed  within 
the  substance  of  the  thyroid,  and  is  then  known  as  the  internal  parathyroid, 
the  other  being  the  external  parathyroid.  They  are  quite  unlike  the  thyroids 
in  structure,  consisting  of  solid  masses  or  columns  of  epithelial-like  cells  which 
are  not  arranged  to  form  acinous  vesicles.  According  to  Schaper,4  these  bodies 
are  not  always  paired,  but  may  have  a  multiple  origin  extending  along  the 
common  carotid  in  the  neighborhood  of  the  thyroids. 

Accessory  Thyroids. — In  addition  to  the  parathyroids,  a  variable  number 
of  accessory  thyroids  have  been  described  by  different  observers,  occurring  in 
the  neck  or  even  as  far  down  as  the  heart.  These  bodies  possess  the  structure 
of  the  thyroid,  and  presumably  have  the  same  function.  After  removal  of 
the  thyroids  they  may  suffice  to  prevent  a  fatal  result. 

Funct ions  of  the  Thyroids  and  Parathyroids. — Very  great  interest  has 
been  excited  within  recent  years  with  regard  to  the  functions  of  the  thyroids. 
In  185b'  Schiff  showed  that  in  dogs  complete  extirpation  of  the  two  thyroids 
i-  followed  by  the  death  of  the  animal  ;  and  within  the  last  few  years  similar 
results  have  been  obtained  by  numerous  observers.  Death  is  preceded  by  a 
number  of  characteristic  symptoms,  such  as  muscular  tremors,  which  may 
pass  into  spasms  and  convulsions,  cachexia,  emaciation,  and  a  more  or  less 
marked  condition  of  apathy.  The  muscular  phenomena  seem  to  proceed 
from  the  central  nervous  system,  since  section  of  the  motor  nerves  protects 
the  muscles  from  the  irritation.  The  metabolic  changes  may  also  be  due 
primarily  to  an  alteration  in  the  condition  of  the  cord  and  brain.  Similar 
results  have  been  obtained  in  cats.  Among  the  herbivorous  animals  it 
was  at  first  stated  that  removal  of  the  thyroids  does  not  cause  death;  but 
so  far  as  the  rabbit  is  concerned  Gley5  has  shown  that  if  care  be  taken  to 
remove  the  parathyroids  also,  death  is  as  certain  and  rapid  as  in  the  case 
of  the  carnivora;  a  similar  result  has  been  obtained  upon  rats  by  Chris- 
tiani.     Cases  have  been    reported    in  which  dogs  recovered  after   complete 

1  Berliner  klinisehe  Woehensehrift,  1S88.  2  Archivfiir  Physiologic,  18S9,  Suppl.  Bd. 

5  Pilii'i' r'.<  Archivfiir  <lir  gesammte  Physiologie,  1894,  Bd.  lvi.  S.  1. 

4  Archiv  fur  mikroskopische  Anatomte,  1895,  Bd.  xlvi.  S.  500. 

5  Archives  de  Physiologie  normal*  et  pathotogique,  1892,  p.  135. 


SECRETION.  269 

thyroidectomy,  but  these  cases  are  rare  and  may  be  explained  probably  by 
the  presence  of  accessory  thyroids  which  remain  after  the  operation.  It  has 
been  observed,  too,  that  the  operation  is  more  rapidly  and  certainly  fatal  in 
young  animals  than  in  old  ones.  In  the  monkey  as  well  as  in  man  the  evil 
results  following  the  removal  of  the  glands  develop  more  slowly  than  in  the 
lower  animals,  and  give  rise  to  a  series  of  symptoms  resembling  those  of 
myxcedema  in  man.  Among  these  symptoms  may  be  mentioned  a  pronounced 
anaemia,  diminution  of  muscular  strength,  failure  of  the  mental  powers,  abnor- 
mal dryness  of  the  skin,  loss  of  hairs,  and  a  peculiar  swelling  of  the  subcu- 
taneous connective  tissue.  Physiologists  have  shown  that  in  the  case  of  dogs 
the  fatal  results  following  thyroidectomy  may  be  mitigated  or  entirely  obviated 
by  grafting  a  portion  of  the  gland  under  the  skin  or  in  the  peritoneal  cavity. 
If  the  piece  grafted  is  sufficiently  large,  the  animal  recovers  apparently  com- 
pletely from  the  operation.  So  also  in  removing  the  thyroids,  if  a  small 
portion  of  the  gland,  or  the  parathyroids,  be  left  undisturbed  the  fatal  symp- 
toms do  not  develop.  In  human  beings  suffering  from  myxoedema  as  the 
result  of  loss  of  function  of  the  thyroids  it  has  been  abundantly  shown  that 
injection  of  thyroid  extracts,  or  feeding  the  fresh  gland,  restores  the  indi- 
vidual to  an  approximately  normal  condition.  In  the  earlier  experiments  on 
thyroidectomy  no  distinction  was  made  between  the  effects  of  removal  of  the 
thyroids  and  parathyroids,  although,  as  said  above,  it  was  noticed  that  in 
some  animals  a  fatal  result  failed  to  follow  the  operation  unless  care  was 
taken  to  extirpate  the  parathyroids  as  well  as  the  thyroids.  It  was  supposed 
by  some  that  the  parathyroids  represented  an  immature  or  embryonic  form 
of  thyroid  tissue,  and  that  after  the  removal  of  the  thyroids  the  parathyroids 
took  on  their  function  and  assumed  a  thyroid  structure.  Histological  evi- 
dence seemed  to  favor  this  view,  but  the  latest  physiological  experiments,  on 
the  contrary,  have  indicated  that  the  parathyroids  are  not  to  be  regarded  as 
immature  structures,  but  as  bodies  possessing  a  definite  functional  value,  dis- 
tinct from,  but  not  less  important  than,  that  of  the  thyroids  themselves. 
Moussou,1  whose  work  has  been  confirmed  in  part  by  others,2  makes  the  fol- 
lowing distinction  in  regard  to  the  effect  of  extirpation  of  these  bodies. 
Removal  of  the  thyroids  and  accessory  thyroids  is  followed  by  a  slowly 
developing  general  trophic  disturbance,  a  progressive  cachexia  that  produces 
a  condition  resembling  myxcedema.  Tn  young  animals  the  effect  is  more 
marked  and  causes  a  condition  of  cretinism.  The  animals,  therefore,  may 
survive  complete  thyroidectomy,  for  long  periods  at  least.  Removal  of  all 
the  parathyroids,  on  the  contrary,  is  followed  by  acute  disturbances  and  rapid 
death,  the  Symptoms  being  the  same  as  those  formerly  described  as  resulting 
from  complete  thyroidectomy.  It  would  seem  from  these  results  that  both 
the  thyroids  and  the  parathyroids  play  an  important  part  in  the  general 
metabolism  of  the  body. 

1  Proceedings  of  Fourth  International  Physiological  Congress,  Cambridge,  1S98. 
-<;icy:  Archiv  fur  die gesammte  Physiologie,  1897,  Bd.  lxvi.  S.  :>08. 


270  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

Two  views  prevail  as  to  the  general  nature  of  their  function.1  According 
to  some,  the  office  of  these  bodies  is  to  remove  some  toxic  substance  or  sub- 
stances which  normally  accumulate  in  the  blood  as  the  result  of  the  body- 
metabolism.  If  the  thyroids  or  parathyroids  are  extirpated,  the  correspond- 
ing substance  then  increases  in  quantity  and  produces  the  observed  symptoms 
by  a  process  of  auto-intoxication.  In  support  of  this  view  there  are  numerous 
observations  to  show  that  the  blood,  or  urine,  or  muscle-juice  of  thyroid- 
ectomized  animals  has  a  toxic  effect  upon  sound  animals.  These  latter 
results,  however,  do  not  appear  to  be  marked  or  invariable,  and  in  the  hands 
of  some  experimenters  have  failed  altogether.  The  second  view  is  that  the 
thyroids  and  parathyroids  secrete  each  a  material,  a  true  internal  secretion, 
which  after  getting  into  the  blood  plays  an  important  and  indeed  essential 
part  in  the  metabolic  changes  of  some  or  all  of  the  organs  of  the  body,  but 
especially  the  central  nervous  system.  In  support  of  this  view  we  have 
such  facts  as  these:  Injections  of  properly  prepared  thyroid  extracts  have 
a  beneficial  and  not  an  injurious  influence  ;  there  is  microscopic  evidence  to 
show  that  the  epithelial  cells  participate  actively  in  the  formation  of  the 
colloid  secretion,  and  that  this  secretion  eventually  reaches  the  blood  by  way 
of  the  lymph-vessels;  the  beneficial  material  in  the  thyroid  extracts  may  be 
obtained  from  the  gland  by  methods  which  prove  that  it  is  a  distinct  and 
stable  substance  formed  in  the  gland,  as  we  might  suppose  would  be  the  case 
if  it  formed  part  of  a  definite  secretion.  This  latter  fact,  indeed,  amounts  to 
a  proof  that  the  important  function  of  the  thyroids  is  connected  with  a 
material  secreted  within  its  substance  ;  but  it  may  still  be  questioned,  per- 
haps, whether  this  material  acts  by  antagonizing  toxic  substances  produced 
elsewhere  in  the  bodv  or  by  directly  influencing  the  body  metabolism.  For 
a  more  specific  theory  of  the  functional  value  of  the  thyroids  proposed  by 
('von'-'  reference  must  be  made  to  original  sources.  Much  work  has  been 
done  to  isolate  the  beneficial  material  of  the  thyroid,  particularly  in  relation 
to  the  therapeutic  use  of  the  gland  in  myxoedema  and  goitre.  The  mere  fact 
that  feeding  the  gland  acts  as  well  as  injecting  its  extracts  shows  the  resistant 
nature  of  the  substance,  since  it  is  evidently  not  injured  by  the  digestive 
secretions.  It  has  been  shown  also  by  Baumann3  that  the  gland  material 
may  be  boiled  for  a  long  period  with  10  per  cent,  sulphuric  acid  without 
destroying  the  beneficial  substance.  This  observer  has  succeeded  in  isolating 
from  the  gland  a  substance  to  which  the  name  iodothyrin  is  given,  which  is 
characterized  by  containing  a  relatively  large  percentage  (!'..">  per  cent,  of  the 
dry  weight)  of  iodine,  and  which  preserves  in  large  measure  the  beneficial 
influence  of  thyroid  extracts  in  cases  of  myxoedema  and  parenchymatous 
goitre.  In  the  parathyroid  tissue  the  same  material  is  contained  in  relatively 
larger  quantities.     This  notable  discovery  shows  that  thyroid  tissue  has  the 

1  See  Schaefer:  "Address  on  Physiology,"  annual  meeting  of  the  British  Medical  Associa- 
tion, London,  July-August,  IS').". 

:  Archives  de  Phyaiologie,  1898,  p.  618. 

8  Zeitschrift fur  physwlogische  Chemie,  lx'.'t'.,  Bd.  xxi.  >S.  319. 


SECRETION.  271 

power  of  forming  a  specific  organic  compound  of  iodine,  and  it  is  possible 
that  its  influence  upon  body-metabolism  may  be  connected  with  this  feet 
Baumann  and  Koos  '  state  that  the  iodothyrin  is  contained  within  the  gland 
mainly  in  a  state  of  combination  with  proteid  bodies,  from  which  it  may  be 
separated  by  digestion  with  gastric  juice  or  by  boiling  with  acids.  Most  of 
'the  substance  is  combined  with  an  albuminous  proteid,  while  a  smaller  part 
is  united  with  a  globulin-like  proteid.  There  can  be  little  doubt  that 
the  authors  have  succeeded  in  isolating  at  least  one  of  the  really  effective 
substances  of  thyroid  extracts.  If  the  distinction  made  between  the  functions 
of  the  thyroids  and  parathyroids  proves  to  be  correct,  and  if  each  of  these 
glands  exercises  its  functions  by  means  of  an  internal  secretion,  we  may  hope 
that  future  work  will  be  able  to  isolate  the  distinctive  substance  or  Hill- 
stances  characteristic  of  each  gland. 

Adrenal  Bodies. — The  adrenal  bodies — or,  as  they  are  frequently  called 
in  human  anatomy,  the  suprarenal  capsules — belong  to  the  group  of  ductless 
glands.  Their  histology  as  well  as  their  physiology  is  incompletely  known. 
It  was  shown  first  by  Brown-Sequard  (1856)  that  removal  of  these  bodies  is 
followed  rapidly  by  death.  This  result  has  been  confirmed  by  many  experi- 
menters, and  so  far  as  the  observations  go  the  effect  of  complete  removal  is 
the  same  in  all  animals.  The  fatal  effect  is  more  rapid  than  in  the  case  of 
removal  of  the  thyroids,  death  following  the  operation  usually  in  two  to  three 
days,  or,  according  to  some  accounts,  within  a  few  hours.  The  symptoms 
preceding  death  are  great  prostration,  muscular  weakness,  and  marked  dimi- 
nution in  vascular  tone.  These  symptoms  are  said  to  resemble  those  occurring 
in  Addison's  disease  in  man,  a  disease  which  clinical  evidence  has  shown  to  be 
associated  with  pathological  lesions  in  the  suprarenal  capsules.  It  has  been 
expected,  therefore,  that  the  results  obtained  for  thyroid  treatment  of  myx- 
cederna  might  be  repeated  in  cases  of  Addison's  disease  by  the  use  of  adrenal 
extracts.  These  expectations  seem  to  have  been  realized  in  part,  but  complete 
and  satisfactory  reports  are  yet  lacking.  The  physiology  of  the  adreuals  has 
usually  been  explained  upon  the  auto-intoxication  theory.  The  death  that  comes 
after  their  removal  has  been  accounted  for  upon  the  supposition  that  during 
life  they  remove  or  destroy  a  toxic  substance  produced  elsewhere  in  the  body, 
possibly  in  the  muscular  system.  Oliver2  and  Sehaefer,  and,  about  the  same 
time,  Cybulski  and  Szymonowicz,8  have  given  reasons  for  believing  that  this 
organ  forms  a  peculiar  substance  that  has  a  very  definite  physiological  action 
especially  upon  the  circulatory  system.  They  find  that  aqueous  extracts  of 
the  medulla  of  the  gland  when  injected  into  the  blood  of  ;i  living  animal 
have  a  remarkable  influence  upon  the  heart  and  blood-vessels.  If  the  vagi 
are  intact,  the  adrenal  extracts  cause  a  very  marked  slowing  of  the  heart-beat 
together  with  a  rise  of  blood-pressure.  When  the  inhibiting  fibres  of  the 
vagus  arc  thrown  out  of  action  by  section  or  by  the  use  of  atropin  the  beart- 

1  Zeitschrift  fur  physiologisehe  Chemie,  L896,  Bd,  xxi.  S.  481, 

*  Journal  of  Physiology,  1895,  vol.  xviii.  |>.  'J.'lu. 

3 Archir fiir  die  geeammte  Physiologic,  L896,  Bd.  Ixiv.  S.  !)7. 


272  AN     AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

rate  is  accelerated,  while  the  blood-pressure  is  increased  sometimes  to  an 
extraordinary  extent.  These  facts  are  obtained  with  very  small  doses  of  the 
extracts.  Schaefer  states  that  as  little  as  51  milligrams  of  the  dried  gland 
may  produce  a  maximal  effect  upon  a  dog  weighing  10  kilograms.  The 
effects  produced  by  such  extracts  arc  quite  temporary  in  character.  In  the 
course  of  a  few  minutes  the  blood-pressure  returns  to  normal,  as  also  the 
heart-beat,  showing  that  the  substance  has  been  destroyed  in  some  way  in  the 
body,  although  where  or  how  this  destruction  occurs  is  not  known.  Accord- 
ing to  Schaefer,  the  kidneys  and  the  adrenals  themselves  are  not  responsible 
tor  this  prompt  elimination  or  destruction  of  the  injurious  substance.  The 
constriction  of  the  blood-vessels  seems  to  be  due  to  a  direct  effect  on  the 
muscles  in  the  walls  of  the  vessels,  in  part  at  least,  since  it  is  present  after  de- 
struction of  the  vaso-motor  centre  and  most  or,  indeed,  all  of  the  spinal  cord. 
Several  observers1  have  shown  satisfactorily  that  the  material  producing  this 
effect  is  present  in  perceptible  quantities  in  the  blood  of  the  adrenal  vein,  so 
that  there  can  be  but  little  doubt  that  it  is  a  distinct  internal  secretion  of  the 
adrenal.  Dreyer  has  shown,  moreover,  that  the  amount  of  this  substance  in 
the  adrenal  blood  is  increased,  judging  from  the  physiological  effects  of 
its  injection,  by  stimulation  of  the  splanchnic  nerve.  Since  this  result  was 
obtained  independently  of  the  amount  of  blood-flow  through  the  gland, 
Dreyer  makes  the  justifiable  assumption  that  the  adrenals  possess  secretory 
nerve  fibres.  Abel2  has  succeeded  in  isolating  the  substance  that  produces 
the  effect  on  blood-pressure  and  heart-rate,  and  proposes  for  it  the  name 
epinephrin.  He  assigns  to  it  the  formula  C17H15N04,  and  describes  it  as  a 
peculiar  unstable  basic  body.  Salts  of  epinephrin  were  obtained  which  when 
injected  into  the  circulation  caused  the  typical  effects  produced  by  injection 
of  extracts  of  the  gland.  It  is  possible  that  the  substance  in  question  may 
be  continually  secreted  under  normal  conditions  by  the  adrenal  bodies  and 
play  a  very  important  part  with  reference  to  the  functional  activity  of  the 
muscular  tissues. 

Pituitary  Body. — This  body  is  usually  described  as  consisting  of  two 
parts,  a  large  anterior  lobe  of  distinct  glandular  structure,  and  a  much  smaller 
posterior  lobe,  whose  structure  is  not  clearly  known,  although  it  contains 
nerve-cells  and  also  apparently  some  glandular  cells.  Embryologically  the 
t\v«>  lobe-  arc  entirely  distinct.  The  anterior  lobe,  which  it  is  preferable  to  call 
the  hypophysis  cerebri,  arises  from  the  epithelium  of  the  mouth,  while  the 
posterior  lobe,  or  the  infundibular  body,  develops  as  an  outgrowth  from  the 
infundibulum  of  the  brain,  and  in  the  adult  remains  connected  with  this 
portion  of  the  brain  by  a  long  stalk.  Howell3  and  others  have  shown  that 
extracts  of  the  hypophysis  when  injected  intravenously  have  little  or  no 
physiological  effect,  while  extracts  of  the  infundibular  body,  on  the  contrary, 

1  American  Journal  of  Physiology,  1899,  vol.  ii.  p.  203. 
'  Zeitsehrtft  fur  phystologisehe  Chemie,  1899,  Bd.  xxviii.  S.  318. 

•  Journal  of  Experimental  Medicine,  1898,  vol.  iii.  p.  245;  also  Schaefer  and  Vincent :  Journal 
of  Physiology,  1899,  vol.  xxv.  p.  87. 


SECRETION.  273 

cause  a  marked  rise  of  blood-pressure  and  slowing  of  the  heart-beat.  These 
effects  resemble  in  general  those  obtained  from  adrenal  extracts,  but  differ  in 
some  details.  They  seem  to  warrant  the  conclusion  that  the  infundibular 
body  is  not  a  mere  rudimentary  organ,  as  has  been  generally  assumed,  but 
produces  a  peculiar  substance,  an  internal  secretion,  that  may  have  a  distinct 
physiological  value.  A  number  of  observers,  especially  Vassale  and  Sacchi, 
have  succeeded  in  removing  the  entire  pituitary  body.  They  report  that  the 
operation  results  eventually  in  the  death  of  the  animal  with  a  certain  group 
of  symptoms,  such  as  muscular  tremors  and  spasms,  apathy  and  dyspnoea,  that 
resemble  the  results  of  thyroidectomy.  It  has  been  suggested  therefore  that 
the  pituitary  body  may  be  related  in  function  to  the  thyroids  and  maybe 
able  to  assume  vicariously  the  functions  of  the  latter  after  thyroidectomy. 
There  is  no  satisfactory  evidence,  however,  in  support  of  this  view.  On  the 
pathological  side  it  has  been  shown  that  usually  lesions  of  the  pituitary  body, 
particularly  of  the  hypophysis,  are  associated  with  a  peculiar  disease  known 
as  acromegaly,  the  most  prominent  symptom  of  which  is  a  marked  hyper- 
trophy of  the  bones  of  the  extremities  and  of  the  face.  The  conclusion  some- 
times drawn  from  this  fact  that  acromegaly  is  caused  by  a  disturbance  of  the 
functions  of  the  pituitary  body  is,  however,  very  uncertain,  and  is  not  sup- 
ported by  any  definite  clinical  or  experimental  facts. 

Testis  and  Ovary. — Some  of  the  earliest  work  upon  the  effect  of  the 
internal  secretions  of  the  glands  was  done  upon  the  reproductive  glands, 
especially  the  testis,  by  Brown-Sequard.1  According  to  this  observer,  extracts 
of  the  fresh  testis  when  injected  under  the  skin  or  into  the  blood  may  have  a 
remarkable  influence  upon  the  nervous  system.  The  general  mental  and 
physical  vigor,  and  especially  the  activity  of  the  spinal  centres,  are  greatly 
improved,  not  only  in  cases  of  general  prostration  and  neurasthenia,  but  also 
in  the  case  of  the  aged.  Brown-Sequard  maintained  that  this  general  dvnamo- 
genic  effect  is  due  to  some  unknown  substance  formed  in  the  testis  and  sub- 
sequently passed  into  the  blood,  although  he  admitted  that  some  of  the  same 
substance  may  be  found  in  the  external  secretion  of  the  testis — i.  c,  the 
spermatic  liquid.  More  recently  Poehl 2  asserts  that  he  has  prepared  a  sub- 
stance, spermin,  to  which  he  gives  the  formula  C5HUN2,  which  has  a  very 
beneficial  effect  upon  the  metabolism  of  the  body.  He  believes  that  this 
spermin  is  the  substance  that  gives  to  the  testicular  extracts  prepared  by 
Brown-Sequard  their  stimulating  effect.  He  claims  for  this  substance  an 
extraordinary  action  as  a  physiological  tonic.  The  precise  scientific  value 
of  the  results  of  experiments  with  the  testicular  extracts  cannot  be  estimated 
at  present,  in  spite  of  the  large  literature  upon  the  subject  ;  we  must  wait 
for  more  detailed  and  exact  experiments,  which  doubtless  will  SOOD  be  made. 
Zoth  ''  and  also  Pregel  'seem  to  have  obtained  exact  objective  proof,  by  means 

1  Archives  de  Plii/^inlni/i,  normale  et  pathologique,  1889  '.>-. 
2 Zeitschriflfiir  klini&che  Wedicin,  1894,  Bd.  xxvi.  S.  133. 

3  Pjiiiger's  Archiv  fiir  die  gesammte  Physiologic,  189(>,   Bd.  Ixii.  S.  335;  also   1897,    Bd.  lxix. 
S.  386.    '  4  Ihid.,  S.  379. 

Vol.  I.— 18 


274  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

of  ergographic  records,  of  the  stimulating  action  of  the  testicular  extracts 
upon  the  neuro-muscular  apparatus  in  num.  They  find  that  injections  of  the 
testicular  extracts  cause  not  only  a  diminution  in  the  muscular  and  nervous 
fatigue  resulting  from  muscular  work,  but  also  lessen  the  subjective  fatigue 
sensations.  The  fact  that  the  internal  secretion  of  the  testis,  if  it  exists  at 
all,  is  not  absolutely  essential  to  the  life  of  the  body  as  a  whole,  as  in  the 
case  «>t'  the  thyroids,  adrenals,  and  pancreas,  naturally  makes  the  satisfactory 
determination  of  its  existence  and  action  a  more  difficult  task. 

Similar  ideas  in  general  prevail  as  to  the  possibility  of  the  ovaries  furnish- 
ing an  internal  secretion  that  plays  an  important  part  in  general  nutrition. 
In  gynecological  practice  it  has  been  observed  that  complete  ovariotomy 
with  its  resulting  premature  menopause  is  often  followed  by  distressing 
symptoms,  mental  and  physical.  In  such  cases  many  observers  have  reported 
that  these  symptoms  may  be  alleviated  by  the  use  of  ovarian  extracts.  So 
also  in  the  natural,  as  well  as  in  the  premature  menopause  following  opera- 
tions, it  is  a  frequent,  though  not  invariable,  result  for  the  individual  to  gain 
noticeably  in  weight.  The  probability  of  an  effect  of  the  ovaries  on  general 
nutrition  is  indicated  also  by  the  interesting  fact  that  in  eases  of  osteomalacia, 
a  disease  characterized  by  softening  of  the  bones,  removal  of  the  ovaries  may 
exert  a  very  favorable  influence  upon  the  course  of  the  disease.  These  indi- 
cations have  found  some  experimental  verification  recently  in  a  research  by 
Loewy  and  Richter1  made  upon  dogs.  These  observers  found  that  complete 
removal  of  the  ovaries,  although  at  first  apparently  without  effect,  resulted 
in  the  course  of  two  to  three  months  in  a  marked  diminution  in  the  consump- 
tion of  oxygen  by  the  animal,  measured  per  kilo,  of  body-weight.  If  now  the 
animal  in  this  condition  was  given  ovarian  extracts  (oophorin  tablets)  the 
amount  of  oxygen  consumed  was  not  only  brought  to  its  former  normal,  but 
considerably  increased  beyond  it.  A  similar  result  was  obtained  when  the 
extracts  were  used  upon  castrated  males.  The  authors  believe  that  their 
experiments  show  that  the  ovaries  form  a  specific  substance  which  is  capable 
of  increasing  the  oxidation  of  the  body. 

Kidney. — Tiegerstedt  and  Bergman2  state  that  a  substance  may  be 
extracted  from  the  kidneys  of  rabbits  which  when  injected  into  the  body  of 
a  living  animal  causes  a  rise  of  blood-pressure.  They  get  the  same  effect  from 
the  blood  of  the  renal  vein.  They  conclude,  therefore,  that  a  substance,  for 
which  they  suggest  the  name  "  rennin,"  is  normally  secreted  by  the  kidney 
into  the  renal  blood,  and  that  this  substance  causes  a  vaso-constriction. 

lArchivfiir  Physiologie,  1899,  Buppl.  Bd.  S.  174. 

2  Skandinavisehes  Archiv  far  Physiologie,  1898,  Bd.  viii.  S.  223;  see  also  Bradford:  Proceedings 
of  the  Royal  Society,  1892. 


V.  CHEMISTRY  OF  DIGESTION  AND  NUTRITION. 


A.    Definition  and  Composition  of  Foods  ;  Nature  of  Enzymes. 

Speaking  broadly,  what  we  eat  and  drink  for  the  purpose  of  nourish- 
ing the  body  constitutes  our  food.  A  person  in  adult  life  who  has  reached 
his  maximum  growth,  and  whose  weight  remains  practically  constant  from 
year  to  year,  must  eat  and  digest  a  certain  average  quantity  of  food  daily  to 
keep  himself  in  a  condition  of  health  and  to  prevent  loss  of  weight.  In 
such  a  case  we  may  say  that  the  food  is  utilized  to  repair  the  wastes  of  the  body 
— that  is,  the  destruction  of  body-material  which  goes  on  at  all  times,  even 
during  sleep,  but  which  is  increased  by  the  physical  and  psychical  activities 
of  the  waking  hours — and  in  addition  it  serves  as  the  source  of  heat,  mechanical 
work,  and  other  forms  of  energy  liberated  in  the  body.  In  a  person  who  is 
growing — one  who  is,  as  we  say,  laying  on  flesh  or  increasing  in  stature — a 
certain  portion  of  the  food  is  used  to  furnish  the  energy  and  to  cover  the  wastes 
of  the  body,  while  a  part  is  converted  into  the  new  tissues  formed  during 
growth.  The  material  that  we  eat  or  drink  as  food  is  for  the  most  part  in  an 
insoluble  form,  or  has  a  composition  differing  very  widely  from  that  of  the 
tissues  which  it  is  intended  to  form  or  to  repair.  The  object  of  the  processes 
of  digestion  carried  on  in  the  alimentary  tract  is  to  change  this  food  so  that 
it  may  be  absorbed  into  the  blood,  and  at  the  same  time  so  to  alter  its  com- 
position that  it  can  be  utilized  by  the  tissues  of  the  body.  For  we  shall  find, 
later  on,  that  certain  foods — eggs,  for  example — which  are  very  nutritious 
when  taken  into  the  alimentary  canal  and  digested  cannot  be  used  at  nil  by 
the  tissues  if  injected  at  once,  unchanged,  into  the  blood.  The  food  of  man- 
kind is  most  varied  iu  character.  At  different  times  of  the  year  and  in 
different  parts  of  the  world  the  diet  is  changed  to  suit  the  necessities  of  the 
environment.  When,  however,  we  come  to  analyze  the  various  animal  and 
vegetable  foods  made  use  of  by  mankind  it  is  found  that  they  arc  all  com- 
posed of  one  or  more  of  five  or  six  different  classes  of  substances  to  which  the 
name  food -.stuff's  or  alimentary  principles  has  been  given.  To  ascertain  the 
nutritive  value  of  any  food,  it  must  he  analyzed  and  the  percentage  amounts 
of  the  different  food-stuffs  contained  in  it  must  be  determined.  The  classi- 
fication of  food-stuffs  usually  given  is  as  follows: 


276  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

Water ; 

[norganic  salts; 

Proteids  (or  proteid-containing  bodies); 
Food-stuffs.  {   Albuminoids  (a  group  of  bodies  resembling  proteids,  but 
having  in  some  respects  a  different  nutritive  value) ; 
Carbohydrates ; 
Fats. 

The  main  facts  with  regard  to  the  specific  nutritive  value  of  each  of  these 
substances  will  be  given  later  on,  after  the  processes  of  digestion  have  been 
described.  A  few  general  remarks,  however,  at  this  place  will  serve  to  give 
the  proper  standpoint  from  which  to  begin  the  study  of  the  chemistry  of 
digestion  and  nutrition. 

Wafer  and  Salts. — Water  and  salts  we  do  not  commonly  consider  as  foods, 
but  the  results  of  scientific  investigation,  as  well  as  the  experience  of  life, 
show  that  these  substances  are  absolutely  necessary  to  the  body.  The  tissues 
must  maintain  a  certain  composition  in  water  and  salts  in  order  to  function 
normally,  and,  since  there  is  a  continual  loss  of  these  substances  in  the  various 
excreta,  they  must  continually  be  replaced  in  some  way  in  the  food.  It  is  to 
be  borne  in  mind  in  this  connection  that  water  and  salts  constitute  a  part  of 
all  our  solid  foods,  so  that  the  body  gets  a  partial  supply  at  least  of  these 
substances  in  everything  we  eat. 

Proteids. — The  composition  and  different  classes  of  proteids  are  described 
from  a  chemical  standpoint  in  the  section  ou  The  Chemistry  of  the  Body. 
Different  varieties  of  proteids  are  found  in  animal  as  well  as  in  vegetable 
foods.  The  chemical  composition  in  all  cases,  however,  is  approximately  the 
same.  Physiologically,  they  are  supposed  to  have  equal  nutritive  values  out- 
side of  differences  in  digestibility,  a  detail  that  will  be  given  later.  The 
essential  use  of  the  proteids  to  the  body  is  that  they  supply  the  material  from 
which  the  new  proteid  tissue  is  made  or  the  old  protcid  tissue  is  repaired, 
although,  as  we  shall  find  when  we  come  to  discuss  the  subject  more  thor- 
oughly (p.  345),  proteids  are  also  extremely  valuable  as  sources  of  energy  to 
the  body.  Inasmuch  as  the  most  important  constituent  of  living  matter  is  the 
proteid  part  of  its  molecule,  it  will  be  seen  at  once  that  proteid  food  is  an 
absolute  necessity.  Proteids  contain  nitrogen,  and  they  arc  frequently  spoken 
of  as  the  nitrogenous  foods;  carbohydrates  and  fats,  on  the  contrary,  do  not 
contain  nitrogen.  It  follows  immediately  from  this  fact  that  fats  and  carbo- 
hydrates alone  could  not  suffice  to  make  new  protoplasm.  If  our  diet  con- 
tained no  proteids,  the  tissue  s  of  the  body  would  gradually  waste  away 
and  death  from  starvation  would  result.  All  the  food-stuffs  are  necessary 
in  one  way  or  another  to  the  preservation  of  perfect  health,  but  proteids, 
together  with  a  certain  proportion  of  water  and  inorganic  salts,  are  absolutely 
necessary  for  the  bare  maintenance  of  animal  life — that  is,  for  the  formation 
and  preservation  of  living  protoplasm.  Whatever  else  is  contained  in  our 
food,  proteid   of  some  kind    must    form    a   part    of  our  diet.     The   use  of 


CHEMISTRY   OF  DIGESTION  AND    NUTRITION.  277 

the  other  food-stuffs  is,  as  we  shall  see,  more  or  less  accessory.  It  may  be 
worth  while  to  recall  here  the  familiar  fact  that  in  respect  to  the  nutritive 
importance  of  proteids  there  is  a  wide  difference  between  animal  and  vegetable 
life.  What  is  said  above  applies,  of  course,  only  to  animals.  Plants  can, 
and  for  the  most  part  do,  build  up  their  living  protoplasm  upon  diets  con- 
taining no  proteid.  With  some  exceptions  that  need  not  be  mentioned  here, 
the  food-stuffs  of  the  great  group  of  chlorophyll-containing  plants,  outside  of 
oxygen,  consist  of  water,  C02,  and  salts,  the  nitrogen  being  found  in  the  last- 
mentioned  constituent. 

Albuminoids. — Gelatin,  such  as  is  found  in  soups  or  is  used  in  the  form  of 
table-gelatin,  is  a  familiar  example  of  the  albuminoids.  They  are  not  found 
to  any  important  extent  in  our  raw  foods,  and  they  do  not  therefore  usually 
appear  in  the  analyses  given  of  the  composition  of  foods.  An  examination  of 
the  composition  and  properties  of  these  bodies  (see  section  on  The  Chemistry 
of  the  Body)  shows  that  they  resemble  closely  the  proteids.  Unlike  the  fats 
and  carbohydrates,  they  contain  nitrogen,  and  they  are  evidently  of  complex 
structure.  Nevertheless,  they  cannot  be  used  in  place  of  proteids  to  build 
protoplasm.  They  are  important  foods  without  doubt,  but  their  value  is  similar 
in  a  general  way  to  that  of  the  non-nitrogenous  foods,  fats  and  carbohydrates, 
rather  than  to  the  so-called  "  nitrogenous  foods,"  the  proteids. 

Carbohydrates. — We  include  among  carbohydrates  the  starches,  sugars, 
gums,  and  the  like  (see  Chemical  section) ;  they  contain  no  nitrogen.  Their 
physiological  value  lies  in  the  fact  that  they  are  destroyed  in  the  body  and  a 
certain  amount  of  energy  is  thereby  liberated.  The  energy  of  muscular  work 
and  of  the  heat  of  the  body  comes  largely  from  the  destruction  or  oxidation 
of  carbohydrates.  Inasmuch  as  we  are  continually  giving  off  energy  from 
the  body,  chiefly  in  the  form  of  muscular  work  and  heat,  it  follows  that 
material  for  the  production  of  this  energy  must  be  taken  in  the  food.  Carbo- 
hydrates form  perhaps  the  easiest  and  cheapest  source  of  this  energy.  They 
constitute  the  bulk  of  our  ordinary  diet. 

Fats. — In  the  group  of  fats  we  include  not  only  what  is  ordinarily  under- 
stood by  the  term,  but  also  the  oils,  animal  and  vegetable,  that  form  such  a 
common  part  of  our  food.  Fats  contain  no  nitrogen  (see  Chemical  section). 
Their  use  in  the  body  is  substantially  the  same  as  that  of  the  carbohydrates. 
Weight  for  weight,  they  arc  more  valuable  than  the  carbohydrates  as  sources 
of  energy,  but  the  latter  are  cheaper,  more  completely  digested  when  i'vd  in 
quantity,  and  more  easily  destroyed  in  the  body.  For  these  reasons  we  find 
that  under  most  conditions  fats  are  a  subsidiary  article  of  food  as  compared 
with  the  carbohydrates.  From  the  standpoint  of  the  physiologist,  fats  arc 
of  special  interest  because  the  animal  body  stores  up  its  reserve  of  food 
material  mainly  in  that  form.  The  history  of  the  origin  of  the  fats  of  the 
body  is  one  of  the  most  interesting  parts  of  the  subject  of  nutrition,  and  it 
will  be  discussed  at  some  length  in  its  proper  place. 

As  has  been  said,  our  ordinary  foods  are  mixtures  of  some  or  all  of  the 
food-stuffs,  together  with  such  things  as  flavors  or  condiments,  whose  nutritive 


278 


AN  AMERICAN   TEXT-BOOK    OF  PHYSIOLOGY. 


value  is  of  a  special  character.  Careful  analyses  have  been  made  of  the 
different  articles  of  food,  mostly  of  the  raw  or  uncooked  foods.  As  might 
be  expected,  the  analyses  on  record  differ  more  or  less  in  the  percentages 
assigned  to  the  various  constituents,  but  almost  any  of  the  tables  published 
give  a  just  idea  of  the  fundamental  nutritive  value  of  the  common  foods. 
For  details  of  separate  analyses  reference  may  be  made  to  some  of  the  larger 
works  upon  the  composition  of  foods.1  The  subjoined  table  is  one  compiled 
by  Munk  from  the  analyses  given  by  Konig: 

Composition  of  Foods. 


In  100  parts. 


Meat 

Egfrs 

(  beese , 

Cow's  milk  .  .  .  , 
Human  milk  .  .  , 
Wheat  Hour  .  .  . 
Wheat  bread  .  .  , 
Rye  flour  .  .  .  , 
Bye  bread    .    .    .    . 

Rice 

Corn , 

Macaroni  .  .  .  . 
Peas,  beans,  lentils 

Potatoes 

Carrots 

( labbages 

Mushrooms  .  .  . 
Fruit 


76.7 
73.7 

36-GO 
87.7 
89.7 
13.3 
35.6 
13.7 
42.3 
13.1 
13.1 
10.1 

12-15 

75.5 

87.1 

90 

73-91 
84 


Proteid. 


Fat. 


20.8 

12.6 

25-33 

3.4 

2.0 

10.2 

7.1 

11.5 

6.1 

7.0 

9.9 

9.0 

23-26 

2.0 

1.0 

2-3 

4-8 

0.5 


1.5 
12.1 
7-30 
3.2 
3.1 
0.9 
0.2 
2.1 
0.4 
0.9 
4.6 
0.3 
l|-2 
0.2 
0.2 
0.5 
0.5 


Carbohydrate. 


Digestible.      Cellulose 


0.3 

3-7 

4.8 

5.0 

74.8 

55.5 

69.7 

49.2 

77.4 

68.4 

79.0 

49-54 

20.6 

9.3 

4-6 

3-12 

10 


0.3 
0.3 
1.6 

0.5 
0.6 
2.5 
0.3 
4-7 
0.7 
1.4 
1-2 
1-5 
4 


Ash. 


1.3 
1.1 
3-4 
0.7 
0.2 
0.5 
1.1 
1.4 
1.5 
1.0 
1.5 
0.5 
2-3 
1.0 
0.9 
1.3 
1.2 
0.5 


An  examination  of  this  table  will  show  that  the  animal  foods,  particularly 
the  meats,  are  characterized  by  their  small  percentage  in  carbohydrate  and  by 
a  relatively  large  amount  of  proteid  or  of  proteid  and  fat.  With  regard  to 
the  last  two  food-stuffs,  meats  differ  very  much  among  themselves.  Some 
idea  of  the  limits  of  variation  may  be  obtained  from  the  following  table, 
taken  chiefly  from    Konig's  analyses: 


Beef,  moderately  fat 

Veal,  fat 

Mutton,  moderately  fat 

J'ork,  lean 

I  [am,  salted 

Pork  (bacon),  very  fat2 
M.nkerel2 


Water. 

Proteid. 

Fat. 

73.03 

20.96 

5.41 

7-J.:;i 

18.88 

7.41 

75.99 

17.11 

5.77 

72.57 

20.05 

6.81 

62.58 

22.32 

s  c,s 

10.00 

3.00 

80.50 

Tl.li 

18.8 

8.2 

Carbohydrate. 


0.46 
0.07 


Ash. 


1.14 

1.33 
1.33 

1.10 
6.42 
6.5 
1.4 


The  vegetable  foods  are  distinguished,  as  a  rule,  by  their  large  percentage 
in  carbohydrates  and  the  relatively  small  amounts  of  proteids  and  fats,  as  seen, 
for  example,  in  the  composition  of  rice,  corn,  wheat,  and  potatoes.     Neverthe- 

1  Konig,  Die  Menscfdichen  Nahrunga  wnd  Gemmmittel,  3d  ed.,  1889;  Parke's  Manual  of  Prac- 
tical Hygiene,  section  on  Food. 

'-'  At  water:   The  Chemistry  of  Foods  ami  Nutrition,  1887. 


CHE3IISTBY   OF  DIGESTION  AND    NUTRITION.  279 

less,  it  will  be  noticed  that  the  proportion  of  proteid  in  some  of  the  vegetables 

is  not  at  all  insignificant.  They  are  characterized  by  their  excess  in  carbohy- 
drates rather  than  by  a  deficiency  in  proteids.  The  composition  of  peas  and 
other  leguminous  foods  is  remarkable  for  the  large  percentage  of  proteid, 
which  exceeds  that  found  in  moats.  Analyses  such  as  arc  given  here  are 
indispensable  in  determining  the  true  nutritive  value  of  foods.  Nevertheless, 
it  must  be  borne  in  mind  that  the  chemical  composition  of  a  food  is  not  alone 
sufficient  to  determine  its  precise  value  in  nutrition.  It  is  obviously  true  that 
it  is  not  what  we  eat,  but  what  we  digest  and  absorb,  that  is  nutritious  to  the 
body,  so  that,  in  addition  to  determining  the  proportion  of  food-stuffs  in  any 
given  food,  it  is  necessary  to  determine  to  what  extent  the  several  constitu- 
ents are  digested.  This  factor  can  be  obtained  only  by  actual  experi- 
ments. It  may  be  said  here,  however,  that  in  general  the  proteids  of  animal 
foods  are  more  completely  digested  than  are  those  of  vegetables,  and  with 
them,  therefore,  chemical  analysis  comes  nearer  to  expressing  directly  the 
nutritive  value. 

The  physiology  of  digestion  consists  chiefly  in  the  study  of  the  chemical 
changes  that  the  food  undergoes  during  its  passage  through  the  alimentary 
canal.  It  happens  that  these  chemical  changes  are  of  a  peculiar  character. 
The  peculiarity  is  due  to  the  fact  that  the  changes  of  digestion  are  effected 
through  the  agency  of  a  group  of  bodies  known  as  enzymes,  or  unorganized 
ferments,  whose  chemical  action  is  more  obscure  than  that  of  the  ordinary 
reagents  with  which  we  have  to  deal.  It  will  save  useless  repetition  to  give 
here  certain  general  facts  that  are  known  with  reference  to  these  bodies, 
reserving  for  future  treatment  the  details  of  the  action  of  the  specific  enzymes 
found  in  the  different  digestive  secretions. 

Enzymes. — Enzymes,  or  unorganized  ferments,  or  unformed  ferments,  is 
the  name  given  to  a  group  of  bodies  produced  in  animals  and  plants,  but  not 
themselves  endowed  with  the  structure  of  living  matter.  The  term  u/norganisu  d 
or  unformed  ferment  was  formerly  used  to  emphasize  the  distinction  between 
these  bodies  and  living  ferments,  such  as  the  yeast-plant  or  the  bacteria. 
"  Enzyme,"  however,  is  a  better  name,  and  is  coming  into  general  use. 
Enzymes  are  to  be  regarded  as  dead  matter,  although  produced  in  living 
protoplasm.  Chemically,  they  are  defined  as  complex  organic  compounds  con- 
taining nitrogen.  Their  exact  composition  is  unknown,  as  ii  has  not  been 
found  possible  heretofore  to  obtain  them  in  pure  enough  condition  for  analysis. 
Although  several  elementary  analyses  are  recorded,  they  cannot  be  considered 
reliable.  It  is  not  known  whether  or  not  the  enzymes  belong  to  the  group  of 
proteids.  Solutions  of  most  of  the  enzymes  give  some  or  all  of  the  general 
reactions  for  proteids,  but  there  is  always  an  uncertainty  as  to  the  purity  <>f 
the  solutions.  With  reference  to  the  fibrin  ferment  of  blood,  one  of  the 
enzymes,  observations  have  recently  been  made  which  seem  to  show  that  it 
belongs  to  the  group  of  combined  proteids,  nucleo-albumins  (for  detail-  -re 
the  section  on  Blood).  But  even  should  this  be  true,  we  arc  not  justified  in 
making  any  general  application  of  this  fact  to  the  whole  group. 


280  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

( 'lassification  of  Enzymes. — Enzymes  are  classified  according  to  the  kind 
of  reaction  they  produce — namely: 

1.  Proteolytic  enzymes,  or  those  acting  upon  proteids,  converting  them  to  a 
soluble  modification,  peptone  or  proteose.  As  examples  of  this  group  we  have 
in  the  animal  body  pepsin  of  the  gastric  juice  and  trypsin  of  the  pancreatic 
juice.  In  plants  a  similar  enzyme  is  found  in  the  pineapple  family  (bromelin) 
and  in  the  papaw  (papain). 

2.  Amylolytic  enzymes,  or  those  acting  upon  the  starches,  converting  them 
to  a  soluble  form,  sugar,  or  sugar  and  dextrin.  As  examples  of  this  group 
we  have  in  the  animal  body  ptyalin,  found  in  saliva,  amylopsin,  found  in 
pancreatic  juice,  and  in  the  liver  an  enzyme  capable  of  converting  glycogen 
to  sugar.  In  the  plants  the  best-known  example  is  diastase,  found  in 
germinating  seeds.  This  particular  enzyme  has  been  known  for  a  long  time 
from  the  use  made  of  it  in  the  manufacture  of  beer.  In  fact,  the  name  "  dias- 
tase "  is  frequently  used  in  a  generic  sense,  "  the  diastatic  enzymes/'  to  cha- 
racterize the  entire  group  of  starch-destroying  ferments. 

3.  Fat-splitting  enzymes,  or  those  acting  upon  the  neutral  fats,  breaking 
them  up  into  glycerin  and  the  corresponding  fatty  acid.  The  best-known 
example  in  the  animal  body  is  found  in  the  pancreatic  secretion;  it  is  known 
usually  as  steapsin,  although  it  has  been  given  several  names.  Similar 
enzymes  are  known  to  occur  in  a  number  of  seeds. 

4.  Sugar-splitting  enzymes,  or  those  having  the  property  of  converting  the 
double  into  the  single  sugars — the  di-saccharides,  such  as  cane-sugar  and 
maltose,  into  the  mono-saccharides,  such  as  dextrose  and  levulose.  Two 
enzymes  of  this  character  are  found  in  the  small  intestine  of  the  animal 
body,  oik;  acting  upon  cane-sugar  and  one  on  maltose.  The  one  acting  on 
cane-sugar  is  known  as  invertine  or  invertase,  while  that  acting  on  maltose 
is  designated  as  maltase. 

5.  Coagulating  enzymes,  or  those  acting  upon  soluble  proteids,  precipitating 
them  in  an  insoluble  form.  As  examples  of  this  class  we  have  fibrin  ferment 
{thrombin),  formed  in  shed  blood,  and  rennin,the  milk-curdling  ferment  of  the 
gastric  juice.    An  enzyme  similar  to  rennin  has  been  found  in  pineapple-juice. 

These  five  classes  comprise  the  chief  groups  of  enzymes  that  are  known  to 
occur  in  the  animal  body.  One  or  more  examples  of  each  group  take  part  in 
the  digestion  of  food  at  some  time  during  its  passage  through  the  alimentary 
canal.  From  time  to  time  other  enzymes  have  been  recognized  in  the  liquids 
or  tissues  of  the  body.1  Thus  in  shed  blood  and  indeed  in  other  tissues  an 
enzyme  (glycolytic  enzyme)  that  i>  capable  of  destroying  sugar  seems  to  be 
present.  When  sugar  is  added  to  shed  blood  it  disappears  as  such,  although 
the  products  formed  have  not  been  recognized.  Similarly  from  many  tissues 
of  the  body  oxidizing  enzymes  have  been  extracted  that  are  capable  of  caus- 
ing energetic  oxidation  of  organic  bodies;  for  instance,  they  can  convert 
salicylaldehyde  to  salicylic  acid.      It  i>  possible  that  these  oxidizing  enzymes, 

1  For  :i  recent  summary  of  tacts  and  literature  upon  enzymes  see  <  rreen  :  The  Soluble  Ferments 
and  Fermt  ntation,  1897. 


CHEMISTRY  OF  DIGESTION  AND  NUTRITION.  281 

or  oxidases,  form  u  group  that  plays  an  important  part  in  the  functional 
metabolism  of  the  tissues,  but  at  present  our  knowledge  of  their  existence 
and  functional  value  in  the  living  organism  is  very  uncertain. 

A  great  number  of  general  reactions  have  been  discovered,  applicable,  with 
an  exception  here  and  there,  to  the  whole  group  of  enzymes.  Among  these 
reactions  the  following  are  the  most  useful  or  significant : 

1.  Solubility. — The  enzymes  are  soluble  in  water.  They  are  also  solu- 
ble in  glycerin,  this  being  the  most  generally  useful  solvent  for  obtaining 
extracts  of  the  enzymes  from  the  organs  in  which  they  are  formed. 

2.  Effect  of  Temperature. — In  a  moist  condition  they  are  destroyed  by 
temperatures  below  the  boiling-point ;  60°  to  80°  C.  are  the  limits  actually 
observed.  Very  low  temperatures  retard  or  even  suspend  entirely  (0°  C.)  their 
action,  without,  however,  destroying  the  enzyme.  For  each  enzyme  there  is 
a  temperature  at  which  its  action  is  greatest. 

3.  Incompleteness  of  Action. — With  the  exception  perhaps  of  the  coagulat- 
ing enzymes,  they  are  characterized  by  the  fact  that  in  any  given  solution  they 
never  completely  destroy  the  substance  upon  which  they  act.  It  seems  that 
the  products  of  their  activity,  as  they  accumulate,  finally  prevent  the  enzymes 
from  acting  further;  when  these  products  are  removed  the  action  of  the  enzyme 
begins  again.  The  most  familiar  example  of  this  very  striking  peculiarity  is 
found  in  the  action  of  pepsin  on  proteids.  The  products  of  digestion  in  this 
case  are  peptones  and  proteoses,  and  when  they  have  reached  a  certain  concen- 
tration they  prevent  any  further  proteolysis  on  the  part  of  the  pepsin. 

4.  Relation  of  the  Amount  of  Enzyme  to  the  Effect  it  Produces. — With  most 
substances  the  extent  of  the  chemical  change  produced  is  proportional  to  the 
amount  of  the  substance  entering  into  the  reaction.  With  the  enzymes  this  is 
not  so.  Except  for  very  small  quantities,  it  may  be  said  that  the  amount  of 
change  caused  is  independent  of  the  amount  of  enzyme  present,  or,  to  state  the 
matter  more  accurately,  "  with  increasing  amounts  of  enzymes  the  extent  of 
action  also  increases,  reaching  a  maximum  with  a  certain  percentage  of  enzyme; 
increase  of  enzyme  beyond  this  has  no  effect."1  This  fact  was  formerly  inter- 
preted to  mean  that  the  enzyme  is  not  used  up — that  is,  not  permanently  altered 
— by  the  reaction  that  it  causes.  This  belief,  indeed,  must  be  true  substan- 
tially, but  it  has  been  found  practically  that  a  given  solution  of  enzyme  cannot 
be  used  over  and  over  again  indefinitely.  It  is  generally  believed  now  that, 
although  an  enzyme  causes  an  amount  of  change  in  the  substance  it  acta  upon 
altogether  out  of  proportion  to  the  amount  of  its  own  substance,  neverthe- 
less it  is  eventually  destroyed;  its  action  is  not  unlimited.  Whether  this  using 
up  of  the  enzyme  is  a  necessary  result  of  its  activity,  or  is,  as  it  were,  an  acci- 
dental effect  from  spontaneous  changes  in  its  own  molecule,  remains  unde- 
termined. 

Theories  of  the  Manner  of  Action  of  the  Enzymes. —  It  is  now  believed 
that  the  action  of  many  of  the  body  enzymes,  especially  the  digestive 
enzymes,  is  that  of  hydrating  agents;  they  produce  their  effeel   by  what   is 

1  Tummumi  :  Zeitechrift fur physiologi&che  Chemie,  1892,  I'.d.  xvi.  S.  '_'7I. 


282  AN  AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

known  as  hydrolysis;  that  is,  they  cause  the  molecules  of  the  substance  upon 
which  they  act  t<>  take  up  one  or  more  molecules  of  water  ;  the  resulting 
molecule  then  splits  or  is  dissociated,  with  the  formation  of  two  or  more  sim- 
pler bodies.  This  is  one  of  the  most  significant  facts  in  connection  with  the 
art  ion  of  the  enzymes;  it  is  well  illustrated  by  the  action  of  invertin  on  cane- 
sugar,  as  follows : 

C12H22Ou+H20  =  C6III206  +  C6H1206 

Cane-sugar.  Dextrose.         Levulose. 

In  what  way  enzymes  cause  the  substances  they  act  upon  to  take  up  water  is 
unknown.  The  fact  that  they  are  not  themselves  used  up  in  the  reaction  pro- 
portionally to  the  change  they  cause  formerly  influenced  physiologists  and  chem- 
ists to  explain  their effeel  as  due  to  catalysis,  or  contact  action.  In  its  original 
sense  this  designation  meant  that  the  molecules  of  enzyme  act  by  their  mere 
presence  or  contiguity,  but  it  need  scarcely  be  said  that  a  statement  of  this 
kind  does  not  amount  to  an  explanation  of  their  manner  of  action  ;  to  say  they 
"act  by  catalysis"  means  nothing  in  itself.  Efforts  to  explain  their  action 
have  resulted  in  a  number  of  hypotheses,  a  detailed  account  of  which  would 
hardly  be  appropriate  here.  It  may  be  mentioned  that  two  ideas  have  found 
most  general  acceptance  :  one,  that  the  enzyme  acts  by  virtue  of  some  peculiar 
physical  property,  such  as  the  physical  state  of  its  molecules,  or  by  setting 
up  vibrations  in  the  molecules  of  the  substance  acted  upon;  the  other  idea 
is  that  the  enzyme  enters  into  a  definite  chemical  reaction,  in  which,  however, 
it  plays  the  part  of  a  carrier  or  go-between,  so  that,  although  the  enzyme  is 
directly  concerned  in  producing  a  chemical  change,  the  final  outcome  is  that  it 
remains  in  its  original  condition.  A  number  of  chemical  reactions  of  this 
general  character  are  known,  in  which  some  one  substance  passes  through  a 
cycle  of  changes,  aiding  in  the  production  of  new  compounds,  but  itself 
returning  always  to  its  first  condition  ;  for  example,  the  part  taken  by  H2S04 
in  the  manufacture  of  ether  from  alcohol,  or  the  successive  changes  of  haemo- 
globin to  oxyhemoglobin  and  back  again  to  haemoglobin  after  giving  up  its 
oxygen  to  the  tissues.  Perhaps  the  most  suggestive  reaction  of  this  character 
is  the  one  quoted  by  Chittenden1  to  illustrate  this  very  hypothesis  as  to  the 
manner  of  action  of  enzymes,  as  follows  :  Oxygen  and  carbon  monoxide  gas, 
if  perfectly  dry,  will  not  react  upon  the  passage  of  an  electric  spark.  If, 
however,  a  little  aqueous  vapor  is  present,  they  may  be  made  to  unite  readily, 
with  the  formation  of  C02.  The  water  in  this  case,  without  doubt,  enters 
into  the  reaction,  but  in  the  end  it  is  re-formed,  and  the  final  result  is  as 
though  the  water  had  not  directly  participated  in  the  process.  The  reaction- 
supposed  to  take  place  are  explained  by  the  following  equations: 

CO  +  2II..O  +  02  =  CO(OH)2  +  H202. 
Ba02  +  GO  =  CX3(OH)2. 

2CO(()H)2  =  2C02  +  2H20. 

1  Cartwright  Lectures,  Medical  Record,  New  York,  April  7,  1894. 


CHE3IISTBY   OF  DIGESTION  AND   NUTRITION.  283 

B.     Salivary  Digestion. 

The  first  of  the  digestive  seeretions  with  which  the  food  comes  in  contact 
is  saliva.  This  liquid  is  a  mixed  secretion  from  the  six  large  salivary  glands 
(parotids,  submaxillaries,  and  sublinguals)  and  the  smaller  mucous  and  serous 
glands  that  open  into  the  mouth.  The  physiological  anatomy  of  these 
glands  and  the  mechanism  by  which  the  secretions  are  produced  and  regulated 
will  be  found  described  fully  in  the  section  on  Secretion  ;  we  are  concerned 
here  only  with  the  composition  of  the  secretion  after  it  is  formed,  and  with  its 
action  upon  foods. 

Properties  and  Composition  of  the  Mixed  Saliva. — Filtered  saliva  is  a 
clear,  viscid,  transparent  liquid.  As  obtained  usually  from  the  mouth,  it  is 
more  or  less  turbid,  owing  to  the  presence  in  it,  in  suspension,  of  particles 
of  food  or  of  detached  cells  from  the  epithelium  of  the  mouth.  A  some- 
what characteristic  cell  contained  in  it  in  small  numbers  is  the  so-called 
"  salivary  corpuscle."  These  bodies  are  probably  leucocytes,  altered  in  struc- 
ture, that  have  escaped  into  the  secretion.  So  far  as  is  known,  they  have  no 
physiological  value.  The  specific  gravity  of  the  mixed  secretion  is  on  an  aver- 
age 1003,  and  its  reaction  is  normally  alkaline.  The  total  amount  of  secretion 
during  twenty-four  hours  varies  naturally  with  the  individual  and  the  condi- 
tions of  life;  the  estimates  made  vary  from  300  to  1500  grams.  Chemically,  in 
addition  to  the  water,  the  saliva  contains  mucin,  ptyalin,  albumin,  and  inor- 
ganic salts.  The  proportions  of  these  constituents  are  given  in  the  following 
analysis  (Hammerbacher) : 

In  1000  parts. 

Water 994.203 

Solids : 

{Mucin  (and  epithelial  cells) 2.202  ^ 
Ptyalin  and  albumin 1.390  V  5.797 
Inorganic  salts 2.205  ) 

Potassium  sulphocyanide 0.041 

The  inorganic  salts,  in  addition  to  the  sulphocyanide,  which  occurs  only  in 
traces,  consist  of  the  chlorides  of  potassium  and  sodium,  the  sulphate  of 
potassium,  and  the  phosphates  of  potassium,  sodium,  calcium,  and  magnesium  ; 
the  earthy  phosphates  form  about  9.6  per  cent,  of  the  total  ash.  Mudn  is  an 
important  constituent  of  saliva;  it  gives  to  the  secretion  its  ropy,  viscid  cha- 
racter, which  is  of  so  much  value  in  the  mechanical  function  it  fulfils  in 
swallowing.  This  substance  is  formed  in  the  salivary  glands.  Its  formation 
in  the  protoplasm  of  the  cells  may  be  followed  microscopically  (see  the  section 
on  Secretion).  Chemically,  it  is  now  known  to  be  a  combination  of  a  proteid 
with  a  carbohydrate  group  (see  section  on  The  Chemistry  of  the  llody).  So 
far  as  known,  mucin  has  no  function  other  than  its  mechanical  use.  The  pres- 
ence of  potassium  sulphocyanide  (K(  !NS)  among  the  salts  of  saliva  has  always 
been  considered  interesting,  since,  although  it  occurs  normally  in  urine  as  well 
as  in  saliva,  it  is  not  a  salt  found  commonly  in  the  secretions  of  the  body,  and 
its  occurrence  in  saliva  seemed  to  indicate  some  special  activity  on  the  pari  of 
the  salivary  gland,  the  possible  value  of  which  has  been  a  subjeel  of  specula- 


284  AN  AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

tion.  In  the  saliva,  however,  the  sulphocyanide  is  found  in  such  minute  traces 
and  its  presence  is  so  inconstant  that  no  special  functional  importance  can  be 
attributed  to  it.  It  is  supposed  to  be  derived  from  the  decomposition  of 
proteids,  and  it  represents,  therefore,  one  of  the  end-products  of  proteid  metab- 
olism. Potassium  sulphocyanide  may  be  detected  in  saliva  by  adding  to  the 
latter  a  dilute  acidulated  solution  of  ferric  chloride,  a  reddish  color  being 
produced. 

Ptyalin  and  its  Action. — From  a  physiological  standpoint  the  most 
important  constituent  of  saliva  is  ptyalin.  It  is  an  unorganized  ferment  or 
enzyme  belonging  to  the  amylolytic  or  diastatic  group  (p.  280)  and  possessing 
the  general  properties  of  enzymes  already  enumerated.  It  is  found  in  human 
saliva  and  in  that  of  many  of  the  lower  animals — for  example,  the  pig  and 
the  herbivora — but  it  is  said  to  be  absent  in  the  carnivora.  Ptyalin  has  not 
been  isolated  in  a  sufficiently  pure  condition  for  satisfactory  analysis,  so  that 
its  chemical  nature  is  undetermined ;  we  depend  for  its  detection  upon  its 
specific  action — that  is,  its  effect  upon  starch.  Speaking  roughly,  we  say  that 
ptvalin  converts  starch  into  sugar,  but  when  we  come  to  consider  the  details 
of  its  action  we  find  that  it  is  complicated  and  that  it  consists  in  a  series  of 
livdrolytic  splittings  of  the  starch  molecule,  the  exact  products  of  the  reaction 
depending  upon  the  stage  at  which  the  action  is  interrupted.  To  demonstrate 
the  action  of  ptyalin  on  starch  it  is  only  necessary  to  make  a  suitable  starch 
paste  by  boiling  some  powdered  starch  in  water,  and  then  to  add  a  little  fresh 
saliva.  If  the  mixture  is  kept  at  a  proper  temperature  (30°  to  40°  C),  the 
presence  of  sugar  may  be  detected  within  a  few  minutes.  The  sugar  that  is 
formed  was  for  a  time  supposed  to  be  ordinary  grape-sugar  (dextrose,  C6H,206), 
but  later  experiments  have  shown  conclusively  that  it  is  maltose  (C12H22On,- 
H2G),  a  form  of  sugar  more  closely  related  in  formula  to  cane-sugar  (see 
Chemical  section).  In  experiments  of  the  kind  just  described  two  facts 
may  easily  be  noticed :  first,  that  the  conversion  of  starch  to  sugar 
is  not  direct,  but  occurs  through  a  number  of  intermediate  stages ;  second, 
that  the  starch  is  not  entirely  converted  to  sugar  under  the  conditions  of 
such  experiments — namely,  when  the  digestion  is  carried  on  in  a  vessel, 
digestion  in  vitro.  The  second  fact  is  an  illustration  of  the  incomplete- 
ly ss  of  action  of  the  enzymes,  a  general  property  that  has  already  been 
noticed.  We  may  suppose,  in  this  as  in  other  cases,  that  the  products  of 
digestion,  as  they  accumulate  in  the  vessel,  tend  to  retard  and  finally  to  sus- 
pend  the  amylolytic  action  of  the  ptyalin.  In  normal  digestion,  however,  it 
is  usually  the  case  that  the  products  of  digestion,  as  they  are  formed,  are 
removed  by  absorption,  and  if  the  above  explanation  of  the  cause  of  the 
incompleteness  of  action  is  correct,  then  under  normal  conditions  we  should 
expect  a  complete  conversion  of  starch  to  sugar.  Lea l  states  that  if  the 
products  of  ptyalin  action  are  partially  removed  by  dialysis  during  digestion 
in  vitro,  a  much  larger  percentage  of  maltose  is  formed.  His  experiments 
would  seem  to  indicate  that  in  the  body  the  action  of  the  amylolytic  ferments 
1  Journal  of  Physiology,  1890,  vol.  xi.  j».  227. 


CHEMISTRY   OF  DIGESTION  AND   NUTRITION.  285 

may  be  complete,  and  that  the  final  product  of  their  action  may  be  maltose 
alone.  It  will  be  found  that  this  statement  applies  practically  not  to  the 
ptyalin,  but  to  the  similar  amylolytic  enzyme  in  the  pancreatic  secretion,  owing 
to  the  fact  that,  normally,  food  is  held  in  the  mouth  for  a  short  time  only,  and 
that  ptyalin  digestion  is  soon  interrupted  after  the  food  reaches  the  stomach. 
With  reference  to  the  intermediate  stages  or  products  in  the  conversion  of 
starch  to  sugar  it  is  difficult  to  give  a  perfectly  clear  account.  It  was  formerly 
thought  that  the  starch  was  first  converted  to  dextrin,  and  this  in  turn  was 
converted  to  sugar.  It  is  now  believed  that  the  starch  molecule,  which  is  quite 
complex,  consisting  of  some  multiple  of  C6H10O5 — possibly  (C6H10O5)20 — first 
takes  up  water,  thereby  becoming  soluble  (soluble  starch,  amylodextrin),  and 
then  splits,  with  the  formation  of  dextrin  and  maltose,  and  that  the  dextrin 
again  undergoes  the  same  hydrolytic  process,  with  the  formation  of  a  second 
dextrin  and  more  maltose;  this  process  may  continue  under  favorable  con- 
ditions until  only  maltose  is  present.  The  difficulty  at  present  is  in  isolating 
the  different  forms  of  dextrin  that  are  produced.  It  is  usually  said  that  at 
least  two  forms  occur,  one  of  which  gives  a  red  color  with  iodine,  and  is  there- 
fore known  as  erythrodextrin,  while  the  other  gives  no  color  reaction  with 
iodine,  and  is  termed  achroodextrin.  It  is  pretty  certain,  however,  that  there 
are  several  forms  of  achroodextrin,  and,  according  to  some  observers,  erythro- 
dextrin also  is  really  a  mixture  of  dextrins  with  maltose  in  varying  propor- 
tions. In  accordance  with  the  general  outline  of  the  process  given  above, 
Neumeister 1  proposes  the  following  schema,  which  is  useful  because  it  gives  a 
clear  representation  of  one  theory,  but  which  must  not  be  considered  as  satis- 
factorily demonstrated  (see  also  the  section  on  Chemistry  of  the  Body). 

r  Maltose. 
/Maltose. 

Erythrodextrin.  < 

/Maltose. 

Achroodextrin  a.  < 

/Maltose. 

Achroodextrin  /3.  / 

/Maltose. 

Achroodextrin  y  ( 
(maltodextrin). ""» 

\Maltose. 

This  schema  represents  the  possibility  of  an  ultimate  conversion  of  all  the 
starch  into  maltose,  and  it  shows  at  the  same  time  that  maltose  may  be  pres- 
ent very  early  in  the  reaction,  and  that  it  may  occur  together  with  one  or  more 
dextrins,  according  to  the  stage  of  the  digestion.  It  should  be  said  in  conclu- 
sion that  this  description  of  the  manner  of  action  of  the  ptyalin  is  supposed  to 
apply  equally  well  to  the  amylolytic  enzyme  of  the  pancreatic  secretion,  the 
two  being,  so  far  as  known,  identical  in  their  properties.  From  the  stand- 
point of  relative  physiological  importance  the  description  of  the  details  of 
amylolytic  digestion  should  have  been  left  until  the  functions  of  the  pancre- 
atic juice  were  considered.  It  is  introduced  here  because,  in  the  Datura!  order 
1  Lehrburh  der  physiologiscken  Chemie,  1893,  p.  232. 


286  AN    AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

of'  treatment,  ptyalin  is  the  first  of  this  group  of  ferments  to  be  encountered. 
It  is  interesting  also  to  remember  in  this  connection  that  starch  can  be  con- 
verted into  sugar  by  a  process  of  hydrolytic  cleavage  by  boiling  with  dilute 
mineral  aeids.  Although  the  general  action  of  dilute  acids  and  of  amylolytic 
enzymes  is  similar,  the  two  processes  are  not  identical,  since  in  the  first  process 
dextrose  is  the  sugar  funned,  while  in  the  second  it  is  maltose.  Moreover, 
variations  in  temperature  affect  the  two  reactions  differently. 

Conditions  Influencing-  the  Action  of  Ptyalin. — Temperature. — As  in 
the  ease  of  the  other  enzymes,  ptyalin  is  very  susceptible  to  changes  of  temper- 
ature. At  0°  C.  its  activity  is  said  to  be  suspended  entirely.  The  intensity 
of  its  action  increases  with  increase  of  temperature  from  this  point,  and 
reaches  its  maximum  at  about  40°  C.  If  the  temperature  is  raised  much 
beyond  this  point,  the  action  of  the  ptyalin  decreases,  and  at  from  65°  to 
70°  C.  the  enzyme  is  destroyed.  In  these  latter  points  ptyalin  differs  from 
diastase,  the  enzyme  of  malt.  Diastase  shows  a  maximum  action  at  50°  C. 
and  is  destroyed  at  80°  C. 

Effect  of  Reaction. — The  normal  reaction  of  saliva  is  slightly  alkaline. 
Chittenden  has  shown,  however,  that  ptyalin  acts  as  well,  or  even  better,  in 
a  perfectly  neutral  medium.  A  strong  alkaline  reaction  retards  or  prevents 
its  action.  The  most  marked  influence  is  exerted  by  acids.  Free  hydrochloric 
acid  to  the  extent  of  only  0.003  per  cent.  (Chittenden)  is  sufficient  to  prac- 
tically stop  the  amylolytic  action  of  enzyme,  and  a  slight  increase  in  acidity  not 
only  stops  the  action,  but  also  destroys  the  enzyme.  The  latter  fact  is  of 
practical  importance  because  it  indicates  that  the  action  of  ptyalin  on  starch 
must  be  suspended  after  the  food  reaches  the  stomach. 

Condition  of  the  Starch. — It  is  a  well-known  fact  that  the  conversion  of  starch 
to  sugar  by  enzymes  takes  place  much  more  rapidly  with  cooked  starch — for 
example,  starch  paste.  In  the  latter  condition  sugar  begins  to  appear  in  a 
lew  minutes  (one  to  four),  provided  a  good  enzyme  solution  is  used.  With 
starch  in  a  raw  condition,  on  the  contrary,  it  may  be  many  minutes,  or  even 
several  hours,  before  sugar  can  be  detected.  The  longer  time  required  for 
raw  starch  is  partly  explained  by  the  well-known  fact  that  the  starch-grains 
are  surrounded  by  a  layer  of  cellulose  or  cellulose-like  material  that  resists 
the  action  of  ptyalin.  When  boiled,  this  layer  breaks  and  the  starch  in  the 
interior  becomes  exposed.  In  addition,  the  starch  itself  is  changed  during  the 
boiling;  it  takes  up  water,  and  in  this  hydrated  condition  is  acted  upon  more 
rapidly  by  the  ptyalin.  The  practical  value  of  cooking  vegetable  foods  is 
evident  from  these  statements  without  further  comment. 

Physiological  Value  of  Saliva. — Although  human  saliva  contains  ptyalin, 
and  this  enzyme  is  known  to  possess  very  energetic  amylolytic  properties,  yet 
it  is  probable  that  it  has  an  insignificant  action  in  normal  digestion.  The  time 
that  food  remains  in  the  mouth  is  altogether  too  short  to  suppose  that  the  starch 
is  profoundly  affected  by  the  ptyalin.  Indeed,  the  saliva  of  dogs  and  cats  is 
said  to  contain  no  ptyalin,  while  horse's  saliva  is  free  from  ptyalin,  although  it 
contains  a  zymogen  that  may  give  rise  to  ptyalin.      it  would  seem  that  what- 


AN  AMERICAN    TENT-BOOK    OE   PHYSIOLOGY.  287 

ever  change  takes  place  must  be  confined  to  the  initial  stages.  After  the  mixed 
saliva  and  food  are  swallowed  it  is  usually  supposed  that  the  acid  reaction  of 
the  gastric  juice  soon  stops  completely  all  further  amylolvtic  action,  although 
this  point  is  often  disputed.1  The  complete  digestion  of  the  carbohydrates 
takes  place  after  the  food  (chyme)  has  reached  the  small  intestine,  under  the 
influence  of  the  amylopsin  of  the  pancreatic  secretion.  For  these  reasons  it  is 
usually  believed  that  the  main  value  of  the  saliva,  to  the  human  being  and  to 
the  carnivora  at  least,  is  that  it  facilitates  the  swallowing  of  food,  it  is  ini pos- 
sible to  swallow  perfectly  dry  food.  The  saliva,  by  moistening  the  food,  not 
only  enables  the  swallowing  act  to  take  place,  but  its  viscous  consistency  must 
aid  also  in  the  easy  passage  of  the  food  along  the  oesophagus.  In  addition 
the  solution  of  parts  of  the  food  in  the  saliva  gives  occasion  for  the  stimula- 
tion of  the  taste  nerves,  and,  as  we  shall  see  in  studying  the  mechanism  of 
gastric  secretion,  the  conscious  sensations  thus  produced  are  very  important 
for  gastric  digestion. 

O.     Gastric  Digestion. 

After  the  food  reaches  the  stomach  it  is  exposed  to  the  action  of  the  secre- 
tion of  the  gastric  mucous  membrane,  known  usually  as  the  gastric  juice.  The 
physiological  mechanisms  involved  in  the  production  and  regulation  of  this 
secretion,  and  the  important  part  played  in  gastric  digestion  by  the  movements 
of  the  stomach,  will  be  found  described  in  other  sections  (Secretion,  Move- 
ments of  Alimentary  Canal).  It  is  sufficient  here  to  say  that  the  secretion 
of  gastric  juice  begins  with  the  entrance  of  food  into  the  stomach.  By  means 
of  the  muscles  of  the  stomach  the  contained  food  is  kept  in  motion  for  several 
hours  and  is  thoroughly  mixed  with  the  gastric  secretion,  which  during  this 
time  is  exerting  its  digestive  action  upon  certain  of  the  food-stuffs.  From  time 
to  time  portions  of  the  liquefied  contents,  known  as  chi/nic,  are  forced  into  the 
duodenum,  and  their  digestion  is  completed  in  the  small  intestine.  Gastric 
digestion  and  intestinal  digestion  go  more  or  less  hand  in  hand,  and  usually 
it  is  impossible  to  tell  in  any  given  case  just  how  much  of  the  food  will 
undergo  digestion  in  the  stomach  and  how  much  will  be  left  to  the  action  of 
the  intestinal  secretions.  It  is  possible,  however,  to  collect  the  gastric  secre- 
tion or  to  make  an  artificial  juice  and  to  test  its  action  upon  food— lull-  In- 
digestions in  vitro.  Much  of  our  fundamental  knowledge  of  the  digestive 
action  of  the  gastric  juice  has  been  obtained  in  this  way,  although  this  has 
been  supplemented,  of  course,  by  numerous  experiments  upon  lower  animals 
and  human   being's. 

Methods  of  Obtaining'  Normal  Gastric  Juice. — The  older  methods  used 
for  obtaining  normal  gastric  juice  were  very  unsatisfactory.  For  instance,  an 
animal  was  made  to  swallow  a  clean  sponge  to  which  a  string  was  attached  so 
that  the  sponge  could  afterward  be  removed  and  its  contents  be  squeezed  out ; 
or  there  was  given  the  animal  to  eat  some  indigestible  material,  to  start  the 
6ecretion  of  juice  by  mechanical  stimulation,  the  animal  being  killed  at  the 
'Austin:  Boston  Medical  and  Surgical  Journal,  1899. 


288  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

proper  time  and  the  contents  of  its  stomach  being  collected.  A  better  method 
of  obtaining  normal  juice  was  suggested  by  the  famous  observations  of  Beau- 
mont1 upon  Alexis  St.  Martin.  St.  Martin,  by  the  premature  discharge  of 
his  gun,  was  wounded  in  the  abdomen  and  stomach.  On  healing,  a  fistulous 
opening  remained  in  the  abdominal  wall,  leading  into  the  stomach,  so  that  the 
contents  of  the  latter  could  be  inspected.  Beaumont  made  numerous  interest- 
ing and  most  valuable  observations  upon  his  patient.  Since  that  time  it  has 
become  customary  to  make  fistulous  openings  into  the  stomachs  of  dogs  when- 
ever it  is  necessary  to  have  the  normal  juice  for  examination.  A  silver  canula 
is  placed  in  the  fistula,  and  at  any  time  the  plug  closing  the  canula  may  be 
removed  and  gastric  juice  be  obtained.  In  some  cases  the  oesophagus  has 
been  occluded  or  excised  so  as  to  prevent  the  mixture  of  saliva  with  the  gastric 
juice.  Gastric  juice  may  be  obtained  from  human  beings  also  in  cases  of  vom- 
iting or  by  means  of  the  stomach-pump,  but  in  such  cases  it  is  necessarily 
more  or  less  diluted  or  mixed  with  food  and  cannot  be  used  for  exact  analyses, 
although  specimens  of  gastric  juice  obtained  by  these  methods  are  valuable  in 
the  diagnosis  and  treatment  of  gastric  troubles. 

Properties  and  Composition  of  Gastric  Juice. — The  normal  gastric  secre- 
tion is  a  thin,  colorless  or  nearly  colorless  liquid  with  a  strong  acid  reaction 
and  a  characteristic  odor.  Its  specific  gravity  varies,  but  it  is  never  great, 
the  average  being  about  1002  to  1003.  Upon  analysis  the  gastric  juice  is 
found  to  contain  a  trace  of  proteid,  probably  a  peptone,  some  mucin,  and 
inorganic  salts,  but  the  essential  constituents  are  an  acid  (HC1)  and  two 
enzymes,  pepsin  and  rennin.  A  satisfactory  analysis  of  the  human  juice  has 
not  been  reported,  owing  to  the  difficulty  of  getting  proper  specimens. 
According  to  Schmidt,2  the  gastric  juice  of  dogs,  free  from  saliva,  has  the 
following  composition,  given  in  1000  parts : 

Water 973.0 

Solids 27.0 

Organic  substances 17.1 

Free  HC1 3.1 

NaCl      2.5 

CaCl, 0.6 

KC1 LI 

NII4C1 0.5 

Ca3(P04)2      1-7 

Mg,,fP04)2 0.2 

FeP04 0.1 

Gastric  juice  docs  not  give  acoagulum  upon  boiling,  but  the  digestive  enzymes 
are  thereby  destroyed.  One  of  the  interesting  facts  about  this  secretion  is  the 
way  in  which  it  withstands  putrefaction.  It  may  be  kept  for  a  long  time,  for 
months  even,  without  becoming  putrid  and  with  very  little  change,  if  any,  in 
its  digestive  action  or  in  its  total  acidity.  This  fact  shows  that  the  juice 
possesses  antiseptic  properties,  and  it  is  usually  supposed  that  the  presence  of 
the  free  acid  accounts  for  this  quality. 

1  Tlte  Phmi'ihujii  of  Digestion,  1833. 

2  Hammarsten:   Text-book  of  Physiological  Chemistry    translated  by  Mandel),  1893,  p.  177. 


CHEMISTRY   OF  DIGESTION   AND   NUTRITION.  289 

The  Acid  of  Gastric  Juice. — The  nature  of  the  free  acid  in  gastric  juice 
was  formerly  the  subject  of  dispute,  some  claiming  that  the  acidity  is  due  to 
HC1,  since  this  acid  can  he  distilled  off  from  the  gastric  juice,  others  contend- 
ing that  an  organic  acid,  lactic  acid,  is  present  in  the  secretion.  All  recent 
experiments  tend  to  prove  that  the  acidity  is  due  to  HC1.  This  fact  was  first 
demonstrated  satisfactorily  by  the  analyses  of  Schmidt,  who  showed  that  if, 
in  a  given  specimen  of  gastric  juice,  the  chlorides  were  all  precipitated  by 
silver  nitrate  and  the  total  amount  of  chlorine  was  determined,  more  was 
found  than  could  be  held  in  combination  by  the  bases  present  in  the  secretion. 
Evidently,  some  of  the  chlorine  must  have  been  present  in  combination  with 
hydrogen  as  hydrochloric  acid.  Confirmatory  evidence  of  one  kind  or  another 
has  since  been  obtained.  Thus  it  has  been  shown  that  a  number  of  color 
tests  for  free  mineral  acids  react  with  the  gastric  juice :  methyl-violet  solutions 
are  turned  blue,  congo-red  solutions  and  test-paper  are  changed  from  red  to 
blue,  00  tropseolin  from  a  yellowish  to  a  pink-red,  and  so  on.  A  number  of 
additional  tests  of  the  same  general  character  will  be  found  described  in  the 
laboratory  handbooks  of  physiology.1  It  must  be  added,  however,  that  lactic  acid 
undoubtedly  occurs,  or  may  occur,  in  the  stomach  during  digestion.  Its  pres- 
ence is  usually  explained  as  being  due  to  the  fermentation  of  the  carbohydrates, 
and  it  is  therefore  more  constantly  present  in  the  stomach  of  the  herbivora. 
The  amount  of  free  acid  varies  according  to  the  duration  of  digestion  ;  that  is, 
the  secretion  does  not  possess  its  full  acidity  in  the  beginning,  owing  probably 
to  the  fact  (Heidenhain)  that  in  the  first  periods  of  digestion,  while  the  secre- 
tion is  still  scanty  in  amount,  a  portion  of  its  acid  is  neutralized  by  the 
swallowed  saliva  and  the  alkaline  secretion  of  the  pyloric  end  of  the  stomach 
(see  the  section  on  Secretion).  Estimates  of  the  maximum  acidity  in  the 
human  stomach  are  usually  given  as  between  0.2  and  <)..">  per  cent.  The 
acidity  of  the  dog's  gastric  juice  is  greater — 0.46  to  <>.."}(;  per  cent.  (  Pawlow). 

Origin  of  the  HC1. — The  gastric  juice  is  the  only  secretion  of  the  body  con- 
taining a  free  acid.  The  fact  that  the  acid  is  a  mineral  acid  makes  this  circum- 
stance more  remarkable,  although  other  instances  of  a  similar  kind  arc  known; 
for  example,  Dolium  galea,  a  mollusc,  secretes  a  salivary  juice  containing  free 
H2S04  and  free  HC1.  When  and  how  the  IIC1  is  formed  in  the  stomach  is 
still  asubject  of  investigation.  Histologically,  attempts  have  been  made  to  show 
that  it  is  produced  in  the  border  cells  of  the  peptic  glands  in  the  fundic  end 
of  the  stomach  (see  Secretion).  It  cannot  be  said,  however,  that  the  evidence 
for  this  theory  is  at  all  convincing;  it  can  be  accepted  only  provisionally. 
Ingenious  efforts  have  been  made  to  determine  the  place  of  production  of  the 
acid  by  micro-chemical  methods.  Substance  thai  give  color  reactions  with 
acids  have  been  injected  into  the  blood,  and  sections  of  the  mucous  membrane 
of  the  stomach  have  then  been  made  to  determine  microscopically  the  part  of 
the  gastric  glands  in  which  the  acid  is  produced  ;  but  beyond  proving  that  the 
acid  is  formed  in  the  mucous  membrane  these  experiments  have  given  negative 
results,  the  color  reaction  for  acid  occurring  throughout  the  thickness  of  the 

1  Stirling  :   Outlines  of  Practiced  Physiology. 
Vol.  I.— 19 


290  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

membrane.1  The  chemistry  of  the  production  of  free  HC1  also  remains  unde- 
termined. No  free  acid  occurs  in  the  blood  or  the  lymph,  and  it  follows,  there- 
fore, that  it  is  manufactured  in  the  secreting  cells.  It  is  quite  evident,  too, 
that  the  source  of  the  acid  is  the  neutral  chlorides  of  the  blood  ;  these  are  in 
some  way  decomposed,  the  chlorine  uniting  with  hydrogen  to  form  HC1  which 
is  turned  out  upon  the  free  surface  of  the  stomach,  while  the  base  remains 
behind  and  probably  passes  back  into  the  blood.  The  latter  part  of  the  pro- 
cess,  the  passage  of  the  base  into  the  blood-current,  enables  us  to  explain  in  part 
the  facts,  noticed  by  a  number  of  observers,  that  the  alkalinity  of  the  blood  is 
increased  and  the  acidity  of  the  urine  is  decreased  after  meals.  Attempts  to 
express  the  reaction  that  takes  place  in  the  decomposition  of  the  chlorides 
are  still  too  theoretical  to  merit  more  than  a  brief  mention  in  a  book  of  this 
character.  According  to  Heidenhain,  the  cells  secrete  a  free  organic  acid, 
which  then  acts  upon  and  decomposes  the  chlorides.  According  to  Maly, 
the  TTC1  is  the  result  of  a  reaction  between  the  phosphates  and  the  chlorides 
of  the  blood,  as  expressed  in  the  two  following  equations: 

NaH2P04  +  NaCl  =  Na2HP04  +  HC1 ;  or, 
3CaCl2  +  2Na2HP04  =  Ca3(P04)2  +  4NaCl  +  2HC1. 

A  recent  theory  by  Liebermann  supposes  that  the  mass  action  of  the  C02 
formed  in  the  tissues  of  the  gastric  mucous  membrane  upon  the  chlorides, 
with  the  aid  of  a  nucleo-albumin  of  acid  properties  that  can  be  isolated 
from  the  gastric  glands,  may  account  for  the  production  of  the  HC1.  Although 
it  is  customary  to  speak  of  the  HC1  as  existing  in  a  free  state  in  the  gastric 
juice,  certain  differences  in  reaction  between  this  secretion  and  aqueous  solu- 
tions of  the  same  acidity  have  led  to  the  suggestion  that  the  HC1,  or  a  part  of 
it  at  least,  is  held  in  some  sort  of  combination  with  the  organic  (proteid)  con- 
stituents of  the  secretion,  so  that  its  properties  are  modified  in  some  minor 
points  just  as  the  properties  of  hemoglobin  are  modified  by  the  combination  in 
which  it  is  held  in  the  corpuscles.  The  differences  usually  described  are  that 
in  the  gastric  juice  or  in  mixtures  of  HC1  and  proteid  the  acid  does  not  dialyze 
nor  distil  off  so  readily  as  in  simple  aqueous  solutions.  The  peptones  and 
proteoses  formed  during  digestion  seem  to  combine  with  the  acid  very  readily 
— so  much  so,  in  fact,  that  in  certain  cases  specimens  of  gastric  juice  taken 
from  the  stomach,  although  they  give  an  acid  reaction  with  litmus-paper,  may 
not  give  the  special  color  reactions  for  free  mineral  acids.  In  such  cases,  how- 
ever, the  acid  may  still  be  able  to  fulfil  its  part  in  the  digestion  of  proteids. 

Nature  and  Properties  of  Pepsin. — Pepsin  is  a  typical  proteolytic  enzyme 
that  exhibits  the  striking  peculiarity  of  acting  only  in  acid  media;  hence 
peptic  digestion  in  the  stomach  is  the  result  of  the  combined  action  of  pepsin 
and  HC1.  Pepsin  is  influenced  in  its  action  by  temperature,  as  is  the  case  with 
the  other  enzymes ;  low  temperatures  retard,  and  may  even  suspend,  its  activity, 
while  high  temperatures  increase  it.  The  optimum  temperature  is  stated  to  be 
from  37°  to  40°  C,  while  exposure  for  some  time  to  80°  C.  results,  when  the 

1  Friinkel :   I'jluger's  Archivfur  die  gesammte Physiologic,  1891,  Bd.  48,  S.  63. 


CHEMISTRY   OF  DIGESTION  AXD   NUTRITION.  291 

pepsin  is  in  a  moist  condition,  in  the  total  destruction  of  the  enzyme.  Pepsin 
has  never  been  isolated  in  sufficient  purity  for  satisfactory  analysis.  It  may  be 
extracted,  however,  from  the  gastric  mucous  membrane  by  a  variety  of  methods 
and  in  different  degrees  of  purity  and  strength.  The  commercial  preparations  of 
pepsin  consist  usually  of  some  form  of  extract  of  the  gastric  mucous  membrane 
to  which  starch  or  sugar  of  milk  has  been  added.  Laboratory  preparations  are 
usually  made  by  mincing  thoroughly  the  mucous  membrane  and  then  extract- 
ing for  a  long  time  with  glycerin.  Glycerin  extracts,  if  not  too  much  diluted 
with  water  or  blood,  keep  for  an  indefinite  time.  Purer  preparations  of  pepsin 
have  been  made  by  what  is  known  as  "Briicke's  method,"  in  which  the  mucous 
membrane  is  minced  and  is  then  self-digested  with  a  5  per  cent,  solution  of 
phosphoric  acid.  The  phosphoric  acid  is  precipitated  by  the  addition  of  lime- 
water,  and  the  pepsin  is  carried  down  in  the  flocculent  precipitate.  This  pre- 
cipitate, after  being  washed,  is  carried  into  solution  by  dilute  hydrochloric 
acid,  and  a  solution  of  cholesterin  in  alcohol  and  ether  is  added.  The  choles- 
terin  is  precipitated,  and,  as  before,  carries  down  with  it  the  pepsin.  This 
precipitate  is  collected,  carefully  washed,  and  then  treated  repeatedly  with 
ether,  which  dissolves  and  removes  the  cholesterin,  leaving  the  pepsin  in 
aqueous  solution.  This  method  is  interesting  not  only  because  it  gives  the 
purest  form  of  pepsin,  but  also  in  that  it  illustrates  one  of  the  properties  of 
this  enzyme — namely,  the  readiness  with  which  it  adheres  to  precipitates  occur- 
ring in  its  solutions.  Pepsin  illustrates  very  well  two  of  the  general  properties 
of  enzymes  that  have  been  described  (p.  281):  first,  its  action  is  incomplete,  the 
accumulation  of  the  products  of  digestion  inhibiting  further  activity  at  a  certain 
stage;  and,  secondly,  a  small  amount  of  the  pepsin,  if  given  sufficient  time  and 
the  proper  conditions,  will  digest  a  very  large  amount  of  proteid. 

Artificial  Gastric  Juice. — In  studying  peptic  digestion  it  is  not  necessary 
for  all  purposes  to  establish  a  gastric  fistula  to  get  the  normal  secretion.  The 
active  agents  of  the  normal  juice  are  pepsin  and  acid  of  a  proper  strength  ;  and, 
as  the  pepsin  can  be  extracted  and  preserved  in  various  ways,  and  the  1 1  CI  can 
easily  be  made  of  the  proper  strength,  an  artificial  juice  can  be  obtained  at  any 
time  which  may  be  used  in  place  of  the  normal  secretion  for  many  purposes.  In 
laboratory  experiments  it  is  customary  to  employ  a  glycerin  extract  of  the  gasl  ric 
mucous  membrane,  and  to  add  a  small  portion  of  this  extract  to  a  large  bulk  of 
0.2  per  cent.  1 101.  The  artificial  juice  thus  made,  when  kept  at  a  temperature  of 
from  37°  to  40°  C,  will  digest  proteids  rapidly  if  the  preparation  of  pepsin  is  a 
good  one.  While  the  strength  of  the  acid  employed  is  generally  from  0.2  to  0.3 
per  cent.,  digestion  will  take  place  in  solutions  of  greater  or  less  acidity.  Too 
great  or  too  small  an  acidity,  however,  will  retard  the  process;  that  is,  there  is 
for  the  action  of  the  pepsin  an  optimum  acidity  which  lies  somewhere  between 
0.2  and  0.5  percent.  Other  acids  may  be  used  in  place  of  the  IIC1 — for  example, 
nitric,  phosphoric,  or  lactic — although  they  are  not  so  effective,  and  the  opti- 
mum acidity  is  different  for  each;  fur  phosphoric  acid  it  is  given  as  2  percent. 

Action  of  Pepsin-Hydrochloric  Acid  on  Proteids. —  It  has  been  knovvn 
for  a  long  time  that  solid  proteids,  such  as  boiled  egg-,  when  exposed   to  the 


292  AX    AMERICAN   TEXT-BOOK    OF  PHYSIOLOGY. 

action  of  a  normal  or  an  artificial  gastric  juice,  swell  up  and  eventually  pass 
into  solution.  The  soluble  proteid  thus  formed  was  known  not  to  be  coagu- 
lated by  heat ;  it  was  remarkable  also  for  being  more  diffusible  than  other 
forms  of  soluble  proteids,  and  was  further  characterized  by  certain  positive 
and  negative  reactions  that  will  be  described  more  explicitly  farther  on. 
This  end-product  of  digestion  was  formerly  described  as  a  soluble  proteid 
with  properties  fitting  it  for  rapid  absorption,  and  the  name  of  peptone,  was 
given  to  it.  It  was  quickly  found,  however,  that  the  process  was  complicated 
— that  in  the  conversion  to  so-called  "  peptone  "  the  proteid  under  digestiou 
passed  through  a  number  of  intermediate  stages.  The  intermediate  products 
were  partially  isolated  and  were  given  specific  names,  such  as  acid-albumin, 
para  peptone,  and  propeptone.  The  two  latter  names,  unfortunately,  have  not 
always  been  used  with  the  same  meaning  by  authors,  and  latterly  they  have 
fallen  somewhat  into  disuse,  although  they  are  still  frequently  employed  to 
indicate  some  one  or  other  of  the  intermediate  stages  in  the  formation  of  pep- 
tones. The  most  complete  investigation  of  the  products  of  peptic  digestion, 
and  of  proteolytic  digestion  in  general,  we  owe  to  Kiihne  and  to  those  who 
have  followed  along  the  lines  he  laid  down,  among  whom  may  be  mentioned 
Chittenden  and  Neumeister.  Their  work  has  thrown  new  light  upon  the 
whole  subject  and  has  developed  a  new  nomenclature.  In  our  account  of  the 
process  we  shall  adhere  to  the  views  and  terminology  of  this  school,  as  they 
seem  to  be  generally  adopted  in  most  of  the  recent  literature.  It  is  well, 
however,  to  add,  by  way  of  caution,  that  investigations  of  this  character  are 
still  going  on,  and  the  views  at  present  accepted  are  liable,  therefore,  to 
changes  in  detail  as  our  experimental  knowledge  increases.  Without  giving 
the  historical  development  of  Kuhne's  theory,  it  may  be  said  that  at  present 
the  following  steps  in  peptic  digestion  have  been  described:  The  proteid 
acted  upon,  whether  soluble  or  insoluble,  is  converted  first  to  an  acid-albumin 
(see  Chemical  section)  to  which  the  name  syntonin  is  usually  given.  In  arti- 
ficial digestions  the  solid  proteid  usually  swells  first  from  the  action  of  the 
acid,  and  then  slowly  dissolves.  Syntonin  has  the  general  properties  of  acid- 
albumins,  of  which  properties  the  most  characteristic  is  that  the  albumin  is 
precipitated  upon  neutralizing  the  solution  with  dilute  alkali.  If,  in  the  begin- 
ning of  a  peptic  digestion,  the  liquid  is  neutralized,  a  more  or  less  abundant 
precipitate  of  syntonin  will  form,  the  quantity  depending  upon  the  stage  of 
digestion.  Syntonin  in  turn,  under  the  influence  of  the  pepsin,  takes  up 
water  and  undergoes  hydrolytic  cleavage,  with  the  formation  of  several  solu- 
ble proteids  known  together  as  primary  albumoses  or  proteoses?  Each  of  these 
proteids  again  takes  up  water  and  undergoes  cleavage,  with  the  formation  of 
a  second  set  of  soluble  proteids  known  as  secondary  proteoses,  in  contradis- 
tinction to  the  primary  proteoses,  but  to  which   the  specific  name  of  deutero- 

1  The  term  proteose  is  used  by  Bome  authors  in  place  of  the  older  name  <ill>inn<i.<,',  as  it  has  a 
more  general  significance.  According  to  this  usage  the  name  cdbumose  is  given  to  the  proteoses 
formed  from  albumin,  globuhse  to  those  formed  from  globulin,  etc,  while  proteose  is  a  general 
term  applying  to  ihe  intermediate  products  from  any  proteid. 


CHEMISTRY  OF  DIGESTION  AND  NUTRITION.  293 

'proteoses  is  given.  Finally,  the  deutero-proteose,  or  more  properly  the 
deutero-proteoses,  again  undergo  hydrolytic  cleavage,  with  the  formation  of 
what  are  known  as  peptones.  Peptic  digestion  can  go  no  farther  than  the 
formation  of  peptones,  but  we  shall  find  later  that  other  proteolytic  enzymes 
(trypsin,  for  example)  are  capable  of  splitting  up  a  part  of  the  peptones  still 
further.  The  fact  that  trypsin  can  act  upon  only  a  part  of  the  peptone  shows 
that  this  latter  substance  is  either  a  mixture  of  at  least  two  separate  although 
closely- related  peptones,  to  which  the  names  of  anti- peptone  and  hemi^peptcme1 
have  been  given,  or  it  is  a  compound  containing  such  hemi-  and  anti-  groups, 
and  capable,  under  the  action  of  trypsin,  of  splitting,  with  the  formation  of 
hemi-peptone  and  anti-peptone  (Neumeister).  If  wre  consider  peptic  digestion 
alone,  this  distinction  is  unnecessary.  The  final  products  of  peptic  digestion 
are  therefore  spoken  of  usually  simply  as  peptones,  although  the  name  ampho- 
pepdone  is  also  frequently  used  to  emphasize  the  fact  that  two  distinct  varieties 
of  peptone  are  possibly  present.  This  description  of  the  steps  in  peptic 
digestion  may  be  made  more  intelligible  by  the  following  schema,  which  is 
modified  somewhat  from  that  given  by  Neumeister : 2 

This  comparatively  simple  schema  must  not  be  regarded  as  final.  It 
seems  quite  probable  that  further  study  will  show  that  the  process  of  splitting 
is  more  complicated  than  is  here  represented,3  but  provisionally,  at  least,  it 

1  Kiihne's  full  theory  of  proteolytic  digestion  assumes  that  the  original  proteid  molecule 
contains  two  atomic  groups,  the  hemi-  and  the  anti-  group.  Proteolytic  enzymes  split  the  mole- 
cule so  as  to  give  a  hemi-  and  an  anti-  compound,  each  of  which  passes  through  a  proteose  stage 
into  its  own  peptone.     A  condensed  schema  of  the  hypothetical  changes  would  be  as  follows: 

Proteid. 


Anti-albumose.  Hemi-albumose. 

I  I 

Anti-peptone.  Hemi-peptone. 


Ampho-peptone. 

In  the  detailed  description  of  proteolysis  given  above,  primary  and  secondary  proteoses  are  pre- 
sumably, according  to  this  schema,  mixtures  in  varying  proportions  of  hemi-  and  ami- com- 
pounds, or,  in  other  words,  they  are  ampho- proteoses.  No  good  way  of  separating  the  anti- 
from  the  hemi-  compounds  has  been  discovered  except  to  digest  them  with  trypsin.  By  tins 
means  each  compound  is  converted  to  its  proper  peptone,  and  by  the  continued  action  of  the 
trypsin  the  hemi-peptone  is  split  into  much  simpler  bodies  (p.  303),  only  anti-peptone  being  left 
in  solution.  The  conception  of  a  proteid  molecule  with  hemi-  and  anti-  groups  and  the  splitting 
into  hemi- and  anti-albumose  is  mainly  an  inference  backward  from  the  fad  thai  there  are  two 
distinct  peptones,  one  of  which,  hemi-peptone,  is  acted  upon  by  trypsin,  while  the  other  is  not 
so  acted  upon.  The  details  of  the  splitting  of  the  proteid  under  the  influence  of  pepsin  are  still 
further  complicated  by  the  fact  that  in  some  cases  a  part  of  the  proteid  remains  undissolved,  form- 
ing a  highly  resistant  substance  to  which  the  name  antalbumM  has  been  given.  It  has  been  shown 
that  if  this  substance  is  dissolved  in  sodium  carbonate  and  then  siilimittecl  to  the  action  of  trypsin, 

only  anti-peptone  is  formed,  indicating  that  it  contains  none  of  the  hemi-  group.  In  fact,  the  prop- 
erties of  antalbumid  show  that  it  is  a  peculiar  modification  of  the  anti-  group  which  may  arise  <lur- 

ing  the  cleavage  of  the  proteid  molecule,  and  may  vary  greatly  in  quantity  in  different  digestions. 

2  Tjehrbtich  (Icr  i>h)/.<i<ilot/i*rh<  n  ('Inmir,   IS!!.'!,  p.   1ST. 

3 Consult  Zunz:  Zeitsehrift fiir  physiologische  Chemie,  Bd.  28,  8.  132;  and  Tick,  Ibid.,  S.  219. 


294  AN  AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

may  be  used  to  indicate  the  general  nature  of  the  process  and  to  show  some 
of  the  important  details  that  seem  to  be  determined. 

Proteid. 

I 
Syntonin. 


(Primary  proteoses)    =  Proto-proteose.  Hetero-proteose. 

|  I 

(Secondary  proteoses)  =  Deutero- proteose.  Deutero-proteose. 

(Ampho-peptones)       =         Peptone.  Peptone. 

According  to  this  schema,  peptic  digestion,  after  the  syntonin  stage,  consists  in 
a  succession  of  hydrolytic  cleavages  whereby  soluble  proteids  (proteoses  and 
peptones)  are  produced  of  smaller  and  smaller  molecular  weights.  It  is  possi- 
ble, of  course,  that  the  steps  in  this  process  may  be  more  numerous  than  those 
represented  in  the  schema,  but  the  general  nature  of  the  changes  seems  to  be 
established  beyond  question.  Moreover,  it  is  easy  to  understand  that  the 
products  of  digestion  in  any  given  case  will  vary  with  the  stage  at  which  the 
examination  is  made.  Sufficiently  early  in  the  process  one  may  find  mainly 
syntonin,  or  syntonin  and  primary  proteoses ;  later  the  secondary  proteoses 
and  peptones  may  occur  alone  or  with  traces  of  the  first  products.  It  is 
worth  emphasizing  also  that  in  artificial  digestions  with  pepsin,  no  matter  how 
long  the  action  is  allowed  to  go  on,  the  final  product  is  always  a  mixture 
of  peptones  and  proteoses  (deutero-proteose).  Even  when  provision  is 
made  to  dialyze  off  the  peptone  as  it  forms,  thus  simulating  natural  diges- 
tion, the  final  result,  according  to  Chittenden  and  Amerman,1  is  still  a 
mixture  of  proteose  and  peptone.  The  extent  of  peptic  digestion  in  the 
body  will  be  spoken  of  presently  in  connection  with  a  resume'  of  the  physiology 
of  gastric  digestion.  In  general,  it  may  be  said  that  from  a  physiological 
standpoint  the  object  of  the  whole  process  is  to  get  the  proteids  into  a  form 
in  which  they  can  be  absorbed  more  easily.  The  properties  and  reactions  of 
peptones  and  proteoses  will  be  found  stated  in  the  Chemical  section.  It  may 
serve  a  useful  end,  however,  to  give  here  some  of  their  properties,  in  order  to 
emphasize  the  nature  of  the  changes  caused  by  the  pepsin. 

Peptones. — The  name  "  peptones  "  was  formerly  given  to  all  the  products 
of  peptic  digestion  after  it  had  passed  the  syntonin  stage — that  is,  to  the  pro- 
teoses as  well  as  the  true  peptones.  Commercially,  the  word  is  still  used  in  this 
sense,  the  preparations  sold  as  peptones  being  generally  mixtures  of  proteoses  and 
peptones.  True  peptones,  in  the  sense  used  by  Kuhne,  are  distinguished  chem- 
ically by  certain  reactions.  Like  the  proteoses,  they  arc  very  soluble,  they  are 
not  precipitated  by  heating,  and  they  give  a  red  biuret  reaction  (see  Reactions 
of  Proteids,  Chemical  section).  They  are  distinguished  from  the  primary  pro- 
teoses by  not  giving  a  precipitate  with  acetic  acid  and  potassium  ferrocyanide, 
and  from  the  whole  group  of  proteoses  by  the  fact  that  they  are  not  thrown 
down  from  their  solutions  by  the  most  thorough  saturation  of  the  liquid  with 
ammonium  sulphate.  This  last  reaction  gives  the  only  means  for  the  complete 
1  Journal  of  Physiology,  1893,  vol.  xiv.  p.  483. 


CHEMISTRY  OF  DIGESTION   AND    NUTRITION.  295 

separation  of  the  peptones  from  the  proteoses.  The  peptones,  indeed,  niav  be 
defined  as  being  the  products  of  proteolytic  digestion  which  are  n<  it  precipitated 
by  saturation  of  the  liquid  with  ammonium  sulphate.  The  validity  of  this 
reaction  has  been  called  in  question.  It  has  been  pointed  out  that,  although 
the  primary  proteoses  are  readily  precipitated  by  this  salt,  the  deutero-pro- 
teoses,  under  certain  circumstances  at  least,  are  not  precipitated,  and  cannot 
therefore  be  distinguished  or  separated  from  the  so-called  "  true  peptone-."  We 
must  await  further  investigations  before  attempting  to  come  to  any  conclusion 
upon  this  point.  It  is  well  to  bear  in  mind  that  the  change  from  ordinary 
proteid  to  peptone  evidently  takes  place  through  a  number  of  intermediate  steps, 
and  the  word  peptone  is  meant  to  designate  the  final  product.  Whether  this 
final  product  is  a  chemical  individual  with  properties  separating  it  from  all  the 
intermediate  stages  is  perhaps  not  yet  fully  known,  but,  provisionally  at  least,  we 
may  adopt  Kiihne's  definition,  outlined  above,  of  what  constitutes  peptone,  as  it 
seems  to  be  generally  accepted  in  current  literature.  Peptones  are  characterized 
by  their  diffusibility,  and  this  property  is  also  possessed,  although  to  a  less 
marked  extent,  by  the  proteoses.  Recent  work  by  Chittenden,1  in  which  he 
corroborates  results  published  simultaneously  by  Kiihne,  shows  the  following 
relative  diffusibility  of  peptones  and  proteoses.  The  solutions  used  were  approx- 
imately 1  per  cent. ;  they  were  dialyzed  in  parchment  tubes  against  running 
water  for  from  six  to  eight  hours,  and  the  loss  of  substance  was  determined 
and  expressed  in  "percentages  of  the  original  amount.  Proto-proteose  gave  a 
loss  of  5.09  per  cent.;  deutero-proteose,  2.21  per  cent.;  peptone,  11  per  cent. 
Rennin. — In  addition  to  pepsin  the  gastric  secretion  contains  an  enzyme 
that  is  characterized  by  its  coagulating  action  upon  milk.  It  has  long  been 
known  that  milk  is  curdled  by  coming  into  contact  with  the  mucous  membrane 
of  the  stomach.  Dried  mucous  membrane  of  the  calf's  stomach,  when  stirred 
in  with  fresh  milk,  will  curdle  the  latter  with  astonishing  rapidity,  and  this 
property  has  been  utilized  in  the  manufacture  of  cheese.  Hammarsten  discovered 
that  this  action  is  due  to  the  presence  of  a  specific  enzyme  that  exists  ready 
formed  in  the  membrane  of  the  sucking-calf's  stomach,  and  which  is  present 
in  a  preparatory  form  (rennin-zymogen)  in  stomachs  of  all  mammals.  This 
enzyme  has  been  given  several  names;  rennin  seems  preferable  to  any  other, 
and  is  the  term  most  commonly  employed.  Rennin  may  be  obtained  from 
the  stomach  by  self-digestion  of  the  mucous  membrane  or  by  extracting  it 
with  glycerin.  Such  extracts  usually  contain  both  pepsin  and  rennin,  but  the 
two  have  been  separated  successfully,  most  easily  by  the  prolonged  action  of 
a  temperature  of  40°  C.  in  acid  solutions,  which  destroys  the  rennin,  but  not 
the  pepsin.  Good  extracts  of  rennin  cause  clotting  of  milk  with  great  rapidity 
at  a  temperature  of  40°  C,  the  milk  (cow's  milk),  if  undisturbed,  setting  first 
into  a  solid  clot,  which  afterward  shrinks  and  presses  out  a  clear  yellowish 
liquid,  the  whey;  with  human  milk,  however,  the  curd  is  much  less  linn, 
being  deposited  in  the  form  of  loose  flocculi.  The  whole  process  resembles  the 
clotting  of  blood  not  only  in  the  superficial  phenomena,  but  also  in  the 
character  of  the  chemical  changes.  Briefly,  what  happens  is  that  the  rennin 
1  Journal  of  Physiology,  1893,  vol.  xiv.  |».  502. 


290  AN   AMERICAN    TEXT- BOOK    OF  PHYSIOLOGY. 

acts  upon  a  soluble  proteid  in  the  milk  known  usually  as  casein,  but  by  some 
called  "  caseinogen,"  and  changes  this  proteid  to  an  insoluble  modification  which 
is  precipitated  as  the  curd.  The  chemistry  of  the  change  is  not  completely 
understood,  and  there  is  an  unfortunate  want  of  agreement  in  the  terminology 
used  to  designate  the  products  of  the  action.  It  has  been  shown  that,  as  in 
the  case  of  blood,  curdling  cannot  take  place  unless  lime  salts  are  present.  What 
seems  to  occur  is  as  follows:  Caseiu  is  a  complex  substance  belonging  to  the 
group  of  nucleo-proteids,  and  when  acted  upon  by  rennin  it  undergoes  hydro- 
lytie  cleavage,  with  the  formation  of  two  proteid  bodies,  paracasein  and  whey 
proteid.  The  first  of  these  bodies  forms  with  calcium  salts  an  insoluble  com- 
pound which  is  precipitated  as  the  curd;  the  second  remains  behind  in  solu- 
tion in  the  whey.  It  should  be  added  that  casein  is  also  precipitated  from 
milk  by  the  addition  of  an  excess  of  acid.  The  curdling  of  sour  milk  in  the 
formation  of  bonnyclabber  is  a  well-known  illustration  of  this  fact.  When 
milk  stands  for  some  time  the  action  of  bacteria  upon  the  milk-sugar  leads  to 
the  formation  of  lactic  acid,  and  when  this  acid  reaches  a  certain  concentration 
it  causes  the  precipitation  of  the  casein.  One  might  suppose  that  the  curdling 
of  milk  in  the  stomach  is  caused  by  the  acid  present  in  the  gastric  secretion, 
but  it  has  been  shown  that  perfectly  neutral  extracts  of  the  gastric  mucous 
membrane  will   curdle  milk   quite  readily. 

So  far  as  our  positive  knowledge  goes,  the  action  of  rennin  is  confined  to 
milk.  (1asein  constitutes  the  chief  proteid  constituent  of  milk,  and  has  there- 
lore  an  important  nutritive  value.  It  is  interesting  to  find  that  before  its 
peptic  digestion  begins  the  casein  is  acted  upon  by  an  altogether  different 
enzyme.  The  value  of  the  curdling  action  is  not  at  once  apparent,  but  we 
may  suppose  that  casein  is  more  easily  digested  by  .the  proteolytic  enzymes 
alnr  it  has  been  brought  into  a  solid  form.  The  action  of  rennin  goes  no 
further  than  the  curdling;  the  digestion  of  the  curd  is  carried  on  by  the  pep- 
sin, and  later,  in  the  intestines,  by  the  trypsin,  with  the  formation  of  proteoses 
and  peptones  as  in  the  case  of  other  proteids. 

Action  of  Gastric  Juice  on  Carbodydrates  and  Fats. — Human  gastric 
juice  itself  has  no  direct  action  upon  carbohydrates;  that  is,  it  does  not  con- 
tain an  amylolytic  enzyme.  It  is  possible,  nevertheless,  that  some  digestion 
of  carbohydrates  goes  on  in  the  stomach,  for,  as  has  been  seen,  the  masticated 
food  is  thoroughly  mixed  with  saliva  before  it  is  swallowed.  The  portion 
that  enters  the  stomach  in  the  beginning  of  digestion,  when  the  acidity  of  the 
total  content-  is  small  (see  p.  289),  may  continue  to  be  acted  upon  by  the 
ptyalin.  According  to  a  recent  author,1  the  gastric  juice  of  the  dog  contains 
an  amylolytic  enzyme  capable  of  acting  on  starch  even  in  the  presence  of  free 
HC1  (0.5  per  cent.).  This  statement  needs  confirmation,  perhaps,  and  there  is  at 
presenl  no  evidence  of  the  existence  of  a  similar  enzyme  in  the  human  gastric 
secretion.    It  should  be  added,  however,  that  Lusk  -  has  shown  that  cane-sugar 

can  be  inverted  to  dextrose  and  levulose  in  the  stomach.      The  importance  of 

this  process  of  inversion,  and   the  means  by  which  it  is  accomplished,  will  be 

1  Friedenthal:  Arehivfur  Physiologie,  1899;  Suppl.  Bd.  383. 
2Voit:  Zeitsehrifi fur  Biohgie,  1891,  Bd.  xxviii.  S.  269. 


CHEMISTRY  OF  DIGESTION  AND    NUTRITION.  297 

described  more  in  detail  when  speaking  of  the  digestion  of  sugars  in  the  small 
intestine  (p.  308).  Upon  the  fats  also  gastric  juice  has  no  direct  digestive 
action.  According  to  the  best  evidence  at  hand,  neutral  fats  are  not  split  in 
the  stomach,  nor  are  they  emulsified  or  absorbed.  Without  doubt,  the  heat 
of  the  stomach  is  sufficient  to  liquefy  most  of  the  fats  eaten,  and  the  move- 
ments of  the  stomach,  together  with  the  digestive  action  of  its  juice  on  the 
proteids  and  albuminoids  with  which  the  fats  are  often  mixed,  bring  about 
such  a  mechanical  mixture  of  the  fats  and  oils  with  the  other  elements  of  the 
chyme  as  facilitates  the  more  rapid  digestion  of  these  substances  in  the  intestine. 

Action  of  Gastric  Juice  on  the  Albuminoids. — Gelatin  is,  from  a 
nutritive  standpoint,  the  most  important  of  the  albuminoids,  [ts  nutritive 
value  is  stated  briefly  on  page  277.  It  has  been  shown  that  this  substance  is 
acted  upon  by  pepsin  in  a  way  practically  identical  with  that  described  for  the 
proteids.  Intermediate  products  are  formed  similar  to  the  albumoses,  which 
products  have  been  named  gelatoses  or  glutoses;  these  in  turn  may  be  con- 
verted to  gelatin  peptones.  It  is  stated  that  the  action  of  pepsin  is  confined 
almost,  if  not  entirely,  to  changing  gelatin  to  the  gelatose  stage.  The  pro- 
teolytic enzyme  of  the  pancreatic  secretion,  however  carries  the  change  to  the 
peptone  stage  much  more  readily. 

Why  does  the  Stomach  not  Digest  Itself? — The  gastric  secretion  will 
readily  digest  a  stomach  taken  from  some  other  animal,  or  under  certain  con- 
ditions it  may  digest  the  stomach  in  which  it  is  secreted.  If,  for  instance,  an 
animal  is  killed  while  in  full  digestion,  the  stomach  may  undergo  self-diges- 
tion, especially  if  the  body  is  kept  warm.  This  phenomenon  has  been  observed 
in  human  cadavers.  It  has  been  shown  also  that  if  a  portion  of  the  stomach 
is  deprived  of  its  circulation  by  an  embolism  or  a  ligature,  it  may  be  attacked 
by  the  secretion  and  a  perforation  of  the  stomach- wall  may  result.  How, 
then,  under  normal  conditions,  is  the  stomach  protected  from  corrosion  by  its 
own  secretion?  The  question  has  given  rise  to  much  discussion,  and  in  reality 
it  deals  with  one  of  the  fundamental  properties  of  living  matter,  for  the 
same  question  must  be  extended  to  take  in  the  non-digestion  of  the  small 
intestine  by  the  alkaline  pancreatic  secretion,  the  non-digestion  of  the  digestive 
tracts  of  the  invertebrates,  and  the  case  of  the  unicellular  animals  in  which 
there  is  formed  within  the  animal's  protoplasm  a  digestive  secretion  that 
digests  foreign  material,  but  does  not  affect  the  living  substance  of  the  cell. 
In  the  particular  case  under  consideration — namely,  the  protection  of  the 
mammalian  stomach  from  its  own  secretion — explanations  of  the  following 
character  have  been  offered:  It  was  suggested  (Hunter)  that  the  "  principle 
of  life"  in  living  things  protected  them  from  digestion.  This  suggestion 
cannot  be  considered  seriously  at  the  present  day,  since  it  implies  thai  living 
matter  is  the  seat  of  a  special  force,  the  so-called  "  vital  principle,"  different 
from  the  forms  of  energy  acting  upon  matter  in  general.  Appeals  of  this 
kind  to  an  unknown  force  in  explanation  of  the  properties  of  living  matter 
are  not  now  permissible  in  the  science  of  physiology.  Moreover,  it  was 
shown  by  Bernard  that  the  hind  leg  of  a  living  frog  introduced  into  a 
dog's  stomach  through  a  fistula    undergoes  digestion.      The  same  thing   will 


2!ts  AN    AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

happen,  it  may  be  added,  if  the  leg  is  put  into  a  vessel  containing  an  artificial 
gastric  juice  at  the  proper  temperature.  Bernard's  theory  was  that  the  epithe- 
lium of  the  stomach  acts  as  a  protection  to  the  organ,  preventing  the  absorp- 
tion of  the  juice.  Others  believe  that  the  mucus  formed  by  the  gastric  mem- 
brane acts  as  a  protective  covering;  while  still  another  theory  holds  that  the 
alkaline  blood  circulating  through  the  organ  saves  it  from  digestion,  since  it 
neutralizes  the  acid  of  the  secretion  as  fast  as  it  is  absorbed,  and  it  is  known 
that  pepsin  can  digest  only  in  an  acid  medium.  None  of  these  explanations 
is  sufficient.  The  last  explanation  is  unsatisfactory  because  it  does  not  explain 
the  immunity  of  the  small  intestine  from  digestion  by  the  alkaline  pancreatic 
juice,  or  the  protection  of  the  infusoria  from  their  own  digestive  secretion. 
The  mucous  theory  is  inadequate,  as  we  cannot  believe  that  by  this  means  the 
protection  could  be  as  complete  as  it  is;  and,  moreover,  this  theory  does  not 
admit  of  a  general  application  to  other  cases.  The  epithelium  theory  simply 
changes  the  problem  a  little,  as  it  involves  an  explanation  of  the  immunity  of 
the  living  epithelial  cells.  It  is  well  known  that  in  the  dead  stomach  the 
epithelial  lining  is  no  longer  a  protection  against  digestion,  so  that  we  are  led 
to  believe  that  there  is  nothing  peculiar  in  the  composition  of  epithelial  cells, 
as  compared  with  other  tissues,  to  account  for  their  exemption  under  normal 
conditions.  When  we  come  to  consider  all  the  evidence,  nothing  seems  clearer 
than  that  the  protection  of  the  living  tissue  is  in  every  case  due  to  the  proper- 
ties of  its  living  structure.  So  long  as  the  tissue  is  alive,  it  is  protected  from 
the  action  of  the  digesting  secretion,  but  the  ultimate  physical  or  chem- 
ical reason  for  this  property  is  yet  to  be  discovered.  In  the  case  of  the 
mammalian  stomach  it  is  quite  probable  that  the  lining  epithelial  cells  are 
especially  modified  to  resist  the  action  of  the  digestive  secretion,  but,  as  has 
just  been  said,  they  lose  this  property  as  soon  as  they  undergo  the  change 
from  living  to  dead  structure.  The  digestion  of  the  living  frog's  leg  in 
gastric  juice,  and  similar  instances,  do  not  affect  this  general  idea,  since,  as 
Bernard  himself  pointed  out,  what  happens  in  this  case  is  that  the  tissue  is 
first  killed  by  the  acid  and  then  undergoes  digestion.  On  the  other  hand, 
\i  minister  has  shown  that  a  living  frog's  leg  is  not  digested  by  strong  pan- 
creatic extracts  of  weak  alkaline  reaction,  since  under  these  conditions  the 
tissues  are  not  injured  by  the  slightly  alkaline  liquid.  When  it  is  said  that 
the  exemption  of  living  tissues  from  self-digestion  is  due  to  the  peculiarities 
of  their  structure,  it  must  not  be  supposed  that  this  is  equivalent  to  referring 
the  whole  matter  to  the  action  of  a  mysterious  vital  force.  On  the  contrary, 
all  that  is  meant  is  that  the  -tincture  of  living  protoplasmic  material  is  such 
that  the  action  of  the  digestive  secretion  is  prevented,  possibly  because  it  is  not 
absorbed,  this  result  being  the  outcome  of  the  physical  and  chemical  forces 
exhibited  by  matter  with  this  peculiar  structure.  While  a  statement  of  this 
kind  is  not  an  explanation  of  the  facts  in  question,  and  indeed  amounts  to  a 
confession  that  an  explanation  is  not  at  present  possible,  it  at  least  refers  the 
phenomenon  to  the  action  of  known  properties  of  matter. 

General    Remarks    upon    Gastric    Digestion. — From     the     foregoing 


CHEMISTRY   OF  DIGESTION  AND    NUTRITION.  299 

account  it  will  be  seen  that,  speaking  generally,  the  digestive  functions  of  the 
stomach  are  in  part  to  act  chemically  upon  the  proteids,  and  in  part,  by  the 
combined  action  of  its  secretion  and  its  muscular  movements,  to  get  the  food 
into  a  physical  condition  suitable  for  subsequent  digestion  in  the  intestine. 
The  material  sent  out  from  the  stomach  (chyme)  must  be  quite  variable  in 
composition,  but  physically  the  action  of  the  stomach  has  been  such  as  to 
reduce  it  to  a  liquid  or  semi-liquid  consistency.  The  extent  of  the  true 
digestive  action  of  gastric  juice  on  proteids  is  not  now  believed  to  be  so 
complete  as  it  was  formerly  thought  to  be.  Examination  of  the  chyme 
shows  that  it  may  contain  quantities  of  undigested  or  only  partially  digested 
proteid,  complete  digestion  being  effected  in  the  intestines.  Moreover,  arti- 
ficial peptic  digestion  of  proteids  under  the  most  favorable  conditions  shows 
that  only  a  portion  is  ever  converted  to  peptone,  most  of  it  remaining  in  the 
proteose  stage.  It  has  been  suggested,  therefore,  that  gastric  digestion  of 
proteids  is  largely  preparatory  to  the  more  complete  action  of  the  pancreatic 
juice,  whose  enzyme  (trypsin)  has  more  powerful  proteolytic  properties.  In 
accordance  with  this  idea,  it  has  been  shown  that  an  animal  can  live  and 
thrive  without  a  stomach.  Several  cases1  are  on  record  in  which  the  stomach 
was  practically  removed  by  surgical  operations,  the  oesophagus  being  stitched 
to  the  duodenum.  The  animals  did  well  and  seemed  perfectly  normal.  Exper- 
iments of  this  character  do  not,  of  course,  show  that  the  stomach  is  useless  in 
digestion  ;  they  demonstrate  only  that  in  the  animals  used  it  is  not  absolutely 
essential.  The  reason  for  this  will  better  be  appreciated  after  the  digestive 
properties  of  pancreatic  secretion  have  been  studied. 

D.  Intestinal  Digestion. 

After  the  food  has  passed  through  the  pyloric  orifice  of  the  stomach  and  has 
entered  the  small  intestine  it  undergoes  its  most  profound  digestive  changes. 
Intestinal  digestion  is  carried  out  mainly  while  the  food  is  passing  through 
the  small  intestine,  although,  as  we  shall  see,  the  process  is  completed  during 
the  slower  passage  through  the  large  intestine.  Intestinal  digestion  is  effected 
through  the  combined  action  of  three  secretions — namely,  the  pancreatic  juice, 
the  bile,  and  the  intestinal  juice.  The  three  secretions  act  together  upon  the 
food,  but  for  the  sake  of  clearness  it  is  advisable  to  consider  each  one  separately 
as  to  its  properties  and  its  digestive  action. 

Composition  of  Pancreatic  Juice. — Pancreatic  juice  is  the  secretion  of 
the  pancreatic  gland,  in  man  the  main  duet  of  the  gland  opens  into  the 
duodenum,  in  common  with  the  bile-duet,  about  8  to  10  cm.  below  the  opening 
of  the  pylorus.  In  some  of  the  other  mammals  the  arrangement  is  different  : 
in  dogs,  for  example,  there  arc  two  duets,  one  opening  into  the  duodenum, 
together  with  the  bile-duct,  about  3  to  5  cm.  below  the  opening  of  the 
pylorus,  and  one  some  3  to  5  cm.  farther  down.  In  rabbits  the  principal 
duct  opens  separately  into  the  duodenum  about  35  em.  below  the  opening 
of  the  bile-duct.     For  details  as  to  the  act  of  secretion,  its  time-relations  to 

1  Ludwig  and  Ogata/  Archiv  far  Anatomie  urnl  I'ln/sinlogie,  1883,  S.  89;  and  Carvallo  and 
Paction  :  Archives  tic  Physiologie  normal*  et  pathologique,  L894,  p.  100. 


300 


AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 


the  ingestion  of  food,  its  quantity,  etc.,  the  reader  is  referred  to  the  section  on 
Secretion.  Most  of  our  exact  knowledge  of  the  properties  of  the  pancreatic 
secretion  has  been  obtained  either  from  experiments  upon  lower  animals, 
especially  the  dog  and  the  rabbit,  in  which  it  is  possible  to  establish  a  pan- 
creatic fistula  and  to  collect  the  normal  juice,  or  from  experiments  with  arti- 
ficial pancreatic  juice  prepared  from  extracts  of  the  gland.  Various  methods 
have  been  used  in  making  pancreatic  fistulas :  usually  the  main  duct  of  the 
gland,  which  in  the  two  animals  named  is  separate  from  the  bile-duct,  is 
exposed  and  a  canula  is  inserted.  A  better  method,  devised  by  Heidenhain, 
consists  in  .cutting  out  the  piece  of  duodenum  into  which  the  main  duct  opens 
and  sewing  this  isolated  piece  to  the  abdominal  wall  so  as  to  make  a  permanent 
fistula,  the  continuity  of  the  intestinal  tract  in  this  case  being  re-established, 
of  course,  by  sutures.  A  simple  method  of  obtaining  normal  pancreatic  juice 
from  the  rabbit  is  described  by  Ratchford.1  In  his  method  the  portion  of 
the  duodenum  into  which  the  main  duct  opens  is  resected  and  cut  open  along 
the  border  opposite  to  the  mesenteric  attachment.  The  mouth  of  the  duct  is 
seen  as  a  small  papilla  projecting  from  the  surface  of  the  mucous  membrane. 
Through  the  papilla  a  small  glass  canula  may  be  passed  into  the  duct,  and  the 
secretion,  which  flows  slowly,  may  be  collected  for  several  hours.  The  total 
quantity  obtainable  by  this  means  from  a  rabbit  is  small,  but  it  is  sufficient 
for  the  demonstration  of  some  of  the  important  properties  of  pancreatic  juice, 
especially  its  action  upon  fats.  As  obtained  by  these  methods,  the  secretion 
is  found  to  be  a  clear,  colorless,  alkaline  liquid.  The  secretion  obtained 
from  dogs  is  thick  and  glairy,  and  forms  a  coagulum  upon  standing, 
while  that  from  rabbits  is  a  thin,  perfectly  colorless  liquid  which  does  not  form 
a  clot.  In  dogs  the  secretion  from  a  permanent  fistula  soon  becomes  thinner 
than  it  was  when  the  fistula  was  first  established,  and  this  change  in  its  con- 
sistency is  accompanied  by  a  corresponding  variation  in  specific  gravity.  The 
specific  gravity  (dog)  of  the  juice  from  a  temporary  fistula  is  given  at  1030 ; 
from  a  permanent  fistula,  at  1010  to  1011.  The  secretion  coagulates  upon 
being  heated,  owing  to  the  proteids  held  in  solution,  and  it  undergoes  putre- 
faction very  quickly,  so  that  it  cannot  be  kept  for  any  length  of  time.  The 
analysis  of  the  secretion  most  frequently  quoted  is  that  given  by  C.  Schmidt, 
as  follows : 

Pancreatic  Juice  (Dog). 


Constituents. 


\  \V;iter 

"/Solids 

Organic  substances       

Asli 

Sodium  carbonate 

Sodium  chloride 

Calcium,  magnesium,  and  sodium  phosphates 


Immediately  after 

From  permanent 

establishing  fistula. 

fistula. 

900.76 

980.45 

99.24 

19.55 

90.44 

12.71 

8.80 

6.84 

0.58 

3.31 

7.35 

2.50 

0.53 

0.08 

The  composition  of  normal  human  pancreatic  juice  has  not  been  determined 
completely,  owing  to  the  rarity  of  opportunities  of  obtaining  the  secretion, 
1  American  Journal  of  Physiolntji/,  lsii'.i.  vol.  ii.  j>.  -is.",. 


CHEMISTRY  OF  DIGESTION   AND   NUTRITION.  301 

Several  partial  analyses  have  been  reported.  According  to  Zawadsky,1  the 
composition  of  the  secretion  in  a  young  woman  was  as  follows : 

In  1000  parts. 

Water 864.05 

Organic  substances      132.51 

Proteids 92.05 

Salts 3.44 

The  organic  substances  held  in  the  secretion  are  in  part  of  an  albuminous 
nature,  since  they  coagulate  upon  heating,  but  the  exact  nature  of  the  proteid 
or  proteids  has  not  been  determined  satisfactorily.  The  most  important  of  the 
organic  substances — the  essential  constituents,  indeed,  of  the  whole  secretion — 
are  three  enzymes  acting  respectively  upon  the  proteids,  the  carbohydrates, 
and  the  fats.  The  proteolytic  enzyme  is  called  "trypsin;"  the  amvlolvtic 
enzyme  is  described  under  different  names  :  "  amylopsin  "  is  perhaps  the  best, 
and  will  be  adopted  in  this  section ;  for  the  fat-splitting  enzyme  we  shall  use 
the  term  "steapsin."  Owing  to  the  presence  of  these  enzymes  the  pancreatic 
secretion  is  capable  of  exerting  a  digestive  action  upon  each  of  the  three  im- 
portant classes  of  food-stuffs.  It  is  said  that  the  pancreatic  juice  contains 
also  a  coagulating  enzyme,  similar  to  rennin,  capable  of  curdling  milk. 

Trypsin. — Trypsin  is  a  more  powerful  proteolytic  enzyme  than  pepsin. 
Unlike  the  latter,  trypsin  acts  best  in  alkaline  media,  but  it  is  effective  also  in 
neutral  liquids,  or  even  in  solutions  not  too  strongly  acid.  Trypsin  is  affected 
by  changes  in  temperature  like  the  other  enzymes,  its  action  being  retarded 
by  cooling  and  hastened  by  warming.  There  is,  however,  a  temperature, 
that  may  be  called  the  optimum  temperature,  at  which  the  trypsin  acts  most 
powerfully  ;  if,  however,  the  temperature  is  raised  to  as  much  as  70°  to  80°  C, 
the  enzyme  is  destroyed  entirely.  Trypsin  has  never  been  isolated  in  a  condi- 
tion sufficiently  pure  for  analysis,  so  that  its  chemical  composition  is  unknown. 
Extracts  containing  trypsin  can  be  made  from  the  gland  very  easily  and  by 
a  variety  of  methods.  The  usual  laboratory  method  is  to  mince  the  gland  and 
to  cover  it  with  glycerin  for  some  time.  Iu  using  this  and  other  methods  for 
preparing  trypsin  extracts  it  is  best  not  to  take  the  perfectly  fresh  gland,  but 
to  keep  it  for  a  number  of  hours  before  using.  The  reason  for  this  is  that  the 
enzyme  exists  in  the  fresh  gland  in  a  preparatory  stage,  a  zymogen  (see  sec- 
tion on  Secretion),  which  in  this  case  is  called  "  trypsinogen."  Upon  standing, 
the  latter  is  slowly  converted  to  trypsin — a  process  that  may  be  hastened  by 
the  action  of  dilute  acids  and  by  other  means.  An  artificial  pancreatic  juice 
is  prepared  usually  by  adding  a  small  quantity  of  the  pancreatic  extract  to  an 
alkaline  liquid;  the  liquid  usually  employed  is  a  solution  of  sodium  carbonate 
of  from  0.2  to  0.5  per  cent.  To  prevent  putrefactive  changes,  which  come  on 
with  such  readiness  in  pancreatic  digestions,  a  lew  drops  of  an  alcoholic  solution 
of  thymol  may  be  added.  A  mixture  of  this  kind,  if  kept  at  the  proper 
temperature,  digests  proteids  very  rapidly,  and  most  of  our  knowledge  of 
the  action  of  trypsin  has  been  obtained  from  a  study  of  the  products  of  such 
digestions. 

1  Centralblattjur  Physiologie,  1891,  Bd.  v.  S.  179. 


302  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

Products  of  Tryptic  Digestion. — Tryptic  digestion  resembles  peptic  diges- 
tion in  that  proteoses  and  peptones  are  the  chief  products  formed,  but  the  two 
processes  differ  in  a  number  of  details.  The  naked-eye  appearances,  in  the  first 
place,  are  different  in  cases  in  which  the  proteid  acted  upon  is  in  a  solid  form ; 
for  while  in  the  pepsin-hydrochloric  digestion  the  proteid  swells  up  and  grad- 
ually dissolves,  under  the  action  of  trypsin  it  does  not  swell,  but  suffers  erosion, 
as  it  were,  the  solid  mass  of  proteid  being  eaten  out  until  finally  only  the  indi- 
gestible part  remains,  retaining  the  shape  of  the  original  mass,  but  falling  into 
fragments  when  shaken.  In  the  second  place,  the  hydrolytic  cleavages  seem 
to  be  of  a  more  intense  nature.  In  peptic  digestion,  after  the  syntonin  stage  is 
passed,  there  is  a  gradual  change  to  peptone  through  the  intermediate  primary 
and  secondary  proteoses.  Under  the  influence  of  trypsin,  according  to  the  most 
recent  experiments,  the  solid  proteid  undergoes  a  transformation  directly  to 
secondary  proteoses  (deutero-proteoses),  the  intermediate  stages  being  skipped. 
It  was  formerly  thought  that  the  solid  proteid  was  converted  first  into  a  soluble 
proteid,  and  that  if  the  solution  was  alkaline  some  alkali-albumin  was  formed, 
precipitable  by  neutralization,  and  comparable  to  the  syntonin  of  pepsin-hydro- 
chloric digestion.  This  soluble  proteid  was  thought  to  be  split  into  proteoses 
of  the  hemi-  and  anti-  groups  which  were  then  converted  to  the  corresponding 
peptones,  according  to  Kiihne's  schema  (p.  293).  There  seems  to  be  no  doubt 
that  with  the  proteid  most  frequently  used  in  artificial  digestion — namely, 
fibrin  from  coagulated  blood— the  first  effect  is  a  conversion  to  a  soluble 
globulin-like  form  of  proteid  ;  but  Neumeister  finds  that  this  does  not  happen 
with  other  proteids,  and  he  thinks  that  in  the  case  of  fibrin  it  is  not  due  to  a 
true  digestive  action  of  trypsin,  but  to  ;i  partial  solution  of  the  fibrin  by  the 
Inorganic  salts  in  the  liquid.  In  general,  however,  the  preliminary  stage  of 
a  soluble  proteid  is  missed,  as  also  is  that  of  the  primary  proteoses.  The 
proteid  falls  at  once  by  hydrolytic  cleavage  into  deutero-proteoses,  and  these 
in  turn  are  transformed  to  peptones.  Just  at  this  point  comes  in  one  of  the 
most  characteristic  differences  between  the  action  of  pepsin  and  that  of  tryp- 
sin. Pepsin  cannot  affect  the  peptones  further,  but  trypsin  may  act  upon 
the  supposed  hemi-constituent  and  split  it  up,  with  the  formation  of  a  number 
of  much  simpler  nitrogenous  bodies,  most  of  which  are  amido-acids.  The 
final  products  of  prolonged  tryptic  digestion  are,  first,  a  peptone  which  cannot 
further  be  decomposed  by  the  enzyme  and  which  constitutes  what  is  known 
as  anti-peptone?  and,  second,  a  number  of  simpler  organic  substances,  amido- 

1  In  the  account  of  tryptic  digestion  as  in  the  case  of  pepsin  the  nomenclature  of  Kiihne  is 
adhered  to.  It  should  he  staled,  however,  that  of  late  years  some  douht  has  been  thrown  upon 
the  existence  of  an  anti-peptone.  Siegfried  [Ardkiv  fur  Physiologie,  1894)  identifies  it  with  a 
body  to  which  he  <rives  the  name  carnic  acid,  while  Kutseher  (Zeitschrift fur pkysiologische  Chemie, 
lid.  25)  finds  that  anti-peptone  prepared  by  Kiihne's  method  is  at  least  a  mixture,  since  it  con- 
tains the  bases  lysin,  arginin, and  bistidin.  If  it  should  he  shown  that  what  has  been  called 
anti-peptone  is  not  a  peptone  at  all,  but  a  mixture  of  simpler  bodies,  then  it  would  seem  that 
the  original  basis  of  Kiihne's  theory  would  be  destroyed.  There  would  be  no  occasion  for 
supposing  the  existence  of  hemi- and  anti-groupings.  The  general  schema  of  digestion  that  has 
been  developed  by  this  theory,  with  its  stages  of  proteoses  and  peptones,  would  not,  however, 
be  interfered  with. 


CHEMISTRY  OF  DIGESTION  AND  NUTRITION. 


:}03 


acids  and  nitrogenous  bases,  that  come  from  the  splitting  of  that  part  of  the 
peptone  which  can  be  acted  upon  by  the  trypsin,  and  which  constitutes  what 
is  known  as  hemi-peptone.  It  maybe  remarked  in  passing  that  hemi-peptone 
has  not  been  isolated.  Ampho-peptones  containing  both  anti-  and  hemi-pep- 
tones  are  formed  in  peptic  digestion,  and  they  may  be  obtained  from  tryptic 
digestion  if  it  is  not  allowed  to  go  too  far;  anti-peptone,  on  the  other  hand, 
may  be  obtained  from  tryptic  digestion  which  has  been  permitted  to  go  on  until 
the  hemi-peptone  has  been  completely  destroyed,  but  no  good  method  is  known 
by  which  hemi-peptone  can  be  isolated  from  solutions  containing  both  it  and 
the  anti-  form.  The  principal  products  formed  by  the  breaking  up  of  the 
hemi-peptone  molecule  under  the  influence  of  the  trypsin  can  be  formed  in 
the  laboratory  by  processes  that  are  known  to  cause  hydrolytic  decomposi- 
tions. It  is  probable,  therefore,  that  these  substances  may  be  looked  upon  as 
products  of  the  hydrolytic  cleavage  of  hemi-peptone.  They  are  of  smaller 
molecular  weight  and  of  simpler  structure  than  the  peptone  molecule  from 
which  they  are  formed.  A  tabular  list  of  these  bodies,  modified  from  Gam- 
gee,1  is  given.  The  list  includes  only  those  substances  that  have  actually 
been  isolated  ;    it  is  possible  that  others  exist : 

Final  Products  (other  than  Peptones)  of  the  Action  of  Trypsin  on  Albuminous  and  Albuminoid 

Bodies. 


Bodies  derived  from  the 

Organic  body  of  unknown 

fatty  acids. 

Bases. 

composition. 

Aromatic  bodies. 

Iso-butyl  amido-acetic 

Lysin. 

Tryptophan     (gives    a 

Paroxyphenylamidopro- 

acid  (leucin). 

Histidin. 

red  color  on  the  ad- 

pionic acid  (tyrosin). 

Amido  -  valerianic     acid 

Arginin. 

dition    of    chlorine- 

(butalanin). 

Lysatinin. 

water,     and      violet 

Amido-succinic  acid  (as- 

NH8. 

with  bromine-water). 

partic  acid). 

Amido-pyrotartaric  acid 

(glutamic  acid). 

(Diamido-acetic  acid  ?) 

Of  these  substances,  the  ones  longest  known  and  most  easily  isolated  are  leucin 
(C6H,3N02)  and  tyrosin  (C9HnN03).  The  chemical  composition  and  proper- 
ties of  these  and  the  other  products  are  described  in  the  Chemical  section. 
Leucin  and  tyrosin  have  been  found  in  the  contents  of  the  intestines,  and  it  is 
probable,  therefore,  that  the  splitting  of  the  peptone  that  takes  place  so  readily 
in  artificial  tryptic  digestions  occurs  also,  to  some  extent  at  least,  within  the 
body,  although  we  have  no  accurate  estimates  of  the  amount  of  peptone 
destroyed  in  this  way  under  normal  conditions.  On  the  supposition  that  the 
production  of  leucin,  tyrosin,  and  the  other  simple  nitrogenous  bodies  is  a 
normal  result  of  tryptic  digestion  within  the  body,  it  is  interesting  to  inquire 
what  physiological  value,  if  any,  is  to  be  attributed  to  these  substances.  At 
first  sight,  the  formation  of  these  simpler  bodies  from  the  valuable  peptone  would 
seem  to  be  a  waste.  Peptone  we  know  may  be  absorbed  into  the  blood,  and 
may  then  be  w^^\  to  form  or  repair  proteid  tissue,  or  to  furnish  energy  to  the 
1  A  Text-book  of  the  Physiological  Chemistry  of  the  Animal  Body,  1893,  vol.  ii.  p.  230. 


304  AX   AMERICAN    TEXT-BOOK    OE   PHYSIOLOGY. 

bod v  upon  oxidation,  but  leucin  and  tyrosin  and  the  other  products  of  the 
breaking'  up  of  peptone  arc  far  less  valuable  as  sources  of  energy,  and  so  far 
as  we  know  they  cannot  be  used  to  form  or  repair  proteid  tissue.  But  we 
must  be  careful  not  to  jump  too  hastily  to  the  conclusion  that  the  splitting 
of  the  peptone  is  useless.  It  remains  possible  that  a  wider  knowledge  of  the 
subject  may  show  that  the  process  is  of  distinct  value  to  the  body,  although  it 
must  be  confessed  that  no  plausible  suggestion  as  to  its  importance  has  yet 
been  made.  In  addition  to  any  possible  functional  value  which  these  amido- 
bodies  and  nitrogenous  bases  may  possess,  their  occurrence  in  proteolysis  is 
of  immense  interest  to  the  physiologist.  Some  of  them  are  of  a  constitution 
simple  enough  to  be  studied  by  exact  chemical  methods,  and  the  hope  is 
entertained  that  through  them  a  clearer  knowledge  may  be  obtained  of  the 
structure  of  the  proteid  molecule.  It  should  be  added  that  not  only  are  these 
bodies  found  in  the  alimentary  canal  as  products  of  tryptic  digestion,  but 
that  they,  or  some  of  them,  occur  also  in  other  parts  of  the  body,  especially 
under  pathological  conditions,  and  that,  furthermore,  they  occur  among  the 
products  of  the  destruction  of  the  proteid  molecule  by  laboratory  methods  or 
by  the  action  of  bacterial  organisms.  The  different  stages  in  a  complete 
tryptic  digestion  as  outlined  above  are  represented  in  brief  in  the  following 
schema,  modified  from  Neumeister:1 

Proteid. 

I 
Deutero-albumoses. 

Peptone. 


Anti-peptone.  Hemi-peptone. 


Leucin.  Tyrosin.  Aspartic  acid.  Nitrogenous  bases. 


It  may  be  said  in  conclusion  that  trypsin  produces  peptone  from  proteids  more 
readily  than  does  pepsin.  Under  normal  conditions  it  is  probable  that  most 
of  the  proteid  of  the  food  receives  its  final  preparation  for  absorption  in  the 
small  intestine,  under  the  influence  of  this  enzyme. 

Albuminoids. — Gelatin  and  the  other  albuminoids  are  acted  upon  by 
trypsin,  the  products  being  similar  in  general  to  those  formed  from  the  pro- 
teids. As  stated  on  page  2!>7,  pepsin  carries  the  digestion  of  gelatin  mainly  to. 
the  gelatose  stage ;  trypsin,  however,  produces  gelatin  peptones.  It  seems 
probable,  therefore,  that  the  final  digestion  of  the  albuminoids  also  is  effected 
in  the  small  intestine. 

Amylopsin. — The  enzyme  of  the  pancreatic  secretion  that  acts  upon 
starches  is  found  in  extracts  of  the  gland,  made  according  to  the  general 
methods  already  given,  and  its  presence  may  be  demonstrated,  of  course,  in 
the  secretion  obtained  by  establishing  a  pancreatic  fistula.  The  proof  of  the 
existence  of  this  enzyme  is  found  in  the  fact  that  if  some  of  the  pancreatic 
secretion  or  some  of  the  extract  of  the  gland  is  mixed  with  starch  paste,  the 
1  Lehrbuch  der  physiologischen  Chemie,  1S93,  S.  200. 


CHEMISTRY   OF  DIGEST  I  OX   AND   NUTRITION.  305 

starch  quickly  disappears  and  maltose  or  maltose  and  dextrin  are  found 
in  its  place.  Amylopsin  shows  the  general  reactions  of  enzymes  with  rela- 
tion to  temperature,  incompleteness  of  action,  etc.  Its  specific  reaction  is  its 
effect  upon  starches.  Investigation  has  shown  that  the  changes  caused  by  it 
in  the  starches  are  apparently  the  same  as  those  produced  by  ptyalin.  In 
fact,  the  two  enzymes  ptyalin  and  amylopsin  are  identical  in  properties  as 
far  as  our  knowledge  goes,  so  that  it  is  not  uncommon,  in  German  liter- 
ature especially,  to  have  them  both  described  under  the  name  of  ptyalin. 
The  term  amylopsin  is  convenient,  however,  in  any  case,  to  designate  the 
special  origin  of  the  pancreatic  enzyme.  As  to  the  details  of  its  action,  it  is 
unnecessary  to  repeat  what  has  been  said  on  page  285.  The  end-products 
of  its  action,  as  far  as  can  be  determined  from  artificial  digestions,  are  a  sugar, 
maltose  (C^H^Oj^H^O),  and  more  or  less  of  the  intermediate  achroodextrins, 
the  relative  amounts  depending  upon  the  completeness  of  digestion.  As  has 
previously  been  said,  there  are  indications  that  under  the  favorable  conditions 
of  natural  digestion  all  the  starch  may  be  changed  to  maltose,  but  possibly 
it  is  not  necessary  that  the  action  should  be  so  complete  in  order  that  the 
carbohydrate  may  be  absorbed  into  the  blood,  as  will  be  shown  when  we  come 
to  speak  of  the  further  action  of  the  intestinal  secretion  upon  maltose  and  the 
dextrins.  The  amylolytic  action  of  the  pancreatic  juice  is  extremely  import- 
ant. The  starches  constitute  a  large  part  of  our  ordinary  diet.  The  action  of 
the  saliva  upon  them  is  probably,  for  reasons  already  given,  of  subordinate 
importance.  Their  digestion  takes  place,  therefore,  entirely  or  almost  entirely 
in  the  small  intestine,  and  mainly  by  virtue  of  the  action  of  the  amylopsin 
contained  in  the  pancreatic  secretion.  The  action  of  the  amylopsin  is  supple- 
mented to  some  extent,  apparently,  by  a  similar  enzyme  formed  in  small 
quantities  in  the  intestinal  wall  itself,  the  nature  of  which  will  be  described 
presently  in  connection  with  intestinal  secretion. 

Steapsin. — Stcapsin,  or  lipase,  is  the  name  given  to  a  fat-splitting  enzyme 
occurring  in  the  pancreatic  juice.  It  is  of  the  greatest  importance  in  the 
digestion  and  absorption  of  fats.  The  peculiar  power  of  the  pancreatic  juice 
to  >plit  neutral  fats  with  the  liberation  of  free  fatty  acid  was  first  described 
by  Bernard.  His  discovery  has  since  been  corroborated  for  different  animals, 
including  man,  by  the  use  of  normal  pancreatic  juice  obtained  from  a  fistula, 
or  by  the  aid  of  the  tissue  of  the  fresh  gland,  or,  finally,  by  means  of  extracts 
of  the  gland.  When  neutral  fats  (see  Chemical  section  for  the  composition 
of  fats)  are  treated  with  an  extract  containing  steapsin,  they  take  up  water 
and  then  undergo  cleavage  (hydrolysis),  with  the  production  of  glycerin  and 
the  free  fatty  acid  found  in  the  particular  fat  used.  This  reaction  is  explained 
by  the  following  equation,  in  which  a  general  formula  for  l'ats  is  used: 

(:,H5(CnII2n+1COO)3  +  3HzO  =  C3H,(()I  I),  +  3(CJ  I,.,, ,  ,<  !<  )OII). 

Fat.  Glycerin.  Free  fatty  acid. 

The  reaction  in  the  case  of  palmitin  would  be — 

C8H6(CI6H31COO)s+  3H20  =  C,H8(OH)s  +  3(CuH81COOH) 

Palmitin.  Glycerin.  Palmitic  acid. 

Vol.  I.— 20 


306  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

While  this  action  is  undoubtedly  caused  by  an  enzyme,  it  has  not  been  possible 
to  isolate  the  so-called  "steapsin  "  in  a  condition  of  even  approximate  purity. 
As  a  matter  of  fact  also,  ordinary  extracts  of  pancreas,  such  as  the  laboratory 
extracts  in  glycerin,  do  not  usually  show  the  presence  of  this  enzyme  unless 
special  precautions  arc  taken  in  their  preparation.  It  would  seem  that  steapsin 
is  easily  destroyed.  With  fresh  normal  juice  or  with  pieces  of  fresh  pancreas 
the  fat-splitting  effect  can  be  demonstrated  easily.  One  striking  method  of 
making  the  demonstration  is  to  use  hutter  as  the  fat  to  be  decomposed.  If 
butter  is  mixed  with  normal  pancreatic  juice  or  with  pieces  of  fresh  pancreas, 
and  the  mixture  i>  kept  at  the  body-temperature,  the  several  fats  contained  in 
butter  will  be  decomposed  and  the  corresponding  fatty  acids  will  be  liberated, 
among  them  butyric  acid,  which  is  readily  recognized  by  its  familiar  odor, 
that  of  rancid  butter.  'Flic  action  of  steapsin,  as  in  the  case  of  the  other 
enzymes,  is  very  much  influenced  by  the  temperature.  At  the  body-temper- 
ature the  action  is  very  rapid.  The  nature  of  the  fat  also  influences  the 
rapiditv  of  the  reaction;  it  may  be  said,  in  general,  that  fats  with  a  high 
melting-point  are  less  readily  decomposed  than  those  with  a  low  melting- 
point.  It  has  been  shown,  however,  that  even  spermaceti,  which  is  a  body 
related  to  the  fats  and  whose  melting-point  is  53°  C,  is  decomposed,  although 
slowlv  and  imperfectly,  by  steapsin.  The  fat-splitting  action  of  the  steapsin 
undoubtedly  takes  place  normally  in  the  intestines,  but  it  is  cpiestiouable 
whether  all  the  fat  eaten  undergoes  this  process.  In  fact,  it  maybe  said  that 
two  views  are  taught  at  present  regarding  the  digestion  and  absorption  of 
fats.  According  to  the  older  view,  only  a  certain  small  proportion  of  the  fat 
undergoes  splitting,  or  saponification,  as  it  is  sometimes  called.  The  remain- 
der of  the  fat  becomes  emulsified  by  the  products  (fatty  acids)  formed  in  the 
splitting,  and  arc  absorbed  in  an  emulsified  condition  as  neutral  fats.  Accord- 
ing to  the  more  recent  view.1  all  the  fat  is  supposed  to  be  acted  upon  by  the 
steapsin,  with  or  without  previous  cmulsification,  with  the  formation  of 
glycerin  and  fatty  acids.  These  two  products,  the  latter  perhaps  in  part  as  a 
soap  formed  by  reaction  with  the  alkaline  salts  of  the  intestine,  are  absorbed 
in  solution,  and  subsequently  are  recombined,  probably  in  the  substance  of 
the  epithelial  (ills,  to  form  a  neutral  fat  again.  On  both  theories  one  of  the 
first  results  of  the  action  of  the  steapsin  is  the  formation  of  an  emulsion,  the 
value  of  which  on  the  first  theory  is  that  it  brings  the  fat  into  a  form  in 
which  it  can  be  ingested  by  the  epithelial  cells  of  the  villi,  while  on  the 
second  theory  it  consists  in  the  fact  that  by  subdividing  the  fat  globules 
minutely  the  completion  of  the  process  of  saponification  is  hastened.  On  cither 
view,  therefore,  emulsification  is  an  interesting  preliminary  to  the  absorption 
of  fat,  and  some  discussion  of  the  nature  of  the  process  seems  to  be  demanded. 
Emulsification  of  Fats. — An  oil  is  emulsified  when  it  is  broken  up 
into  minute  globules  that  do  not  coalesce,  but  remain  separated  and  more 
or  less  uniformly  distributed  throughout  the  medium  in  which  they  exist. 
Artificial  emulsions  can  be  made  by  shaking  oil  vigorously  in  viscous  solutions 
1  Mo..re  and  Rockwood:  Journal  <>/  Physiology,  1897,  vol.  21,  p.  58. 


CHEMISTRY  OF   DIGESTION   AND   NUTRITION.  307 

of  soap,  mucilage,  etc.  Milk  is  a  natural  emulsion  that  separates  partially 
on  standing,  some  of  the  oil  rising  to  the  top  to  form  cream.  Bernard  made 
the  important  discovery  that  when  oil  and  pancreatic  juice  are  shaken  together 
an  emulsion  of  the  oil  takes  place  very  rapidly,  especially  if  the  temperature 
is  about  that  of  the  body.  The  main  cause  of  the  em  unification  has  been 
shown  to  be  the  formation  of  free  fatty  acids  due  to  the  action  of  steapsin, 
and  the  union  of  these  acids  with  the  alkaline  salts  present  to  form  soaps. 
This  fact  has  been  demonstrated  by  experiments  of  the  following  character: 
If  a  perfectly  neutral  oil  is  shaken  with  an  alkaline  solution  (}  per  cent, 
sodium-carbonate  solution),  no  emulsion  occurs  and  the  two  Liquids  soon  sepa- 
rate. If  to  the  same  neutral  oil  one  adds  a  little  free  fatty  acid,  or  if  one 
uses  rancid  oil  to  begin  with  and  shakes  it  with  \  per  cent,  sodium-carbonate 
solution,  an  emulsion  forms  rapidly  and  remains  for  a  long  time.  Oil  con- 
taining fatty  acids  when  shaken  with  distilled  water  alone  will  not  give  an 
emulsion.  It  has  been  shown,  moreover,  by  Gad  and  Ratchford  that  with  a 
certain  percentage  of  free  fatty  acids  (5J  per  cent.)  rancid  oil  and  a  sodium- 
carbonate  solution  will  form  a  fine  emulsion  spontaneously — that  is,  without 
shaking.  Shakino-  however,  facilitates  the  emulsification  when  the  amount 
of  free  acid  varies  from  this  optimum  percentage.  In  what  May  the  formation 
of  soaps  in  an  oily  liquid  causes  the  oil  to  become  emulsified  is  still  a  matter 
of  speculation.  The  splitting  of  the  oil  into  small  drops  seems  to  be  caused, 
in  cases  of  spontaneous  emulsification,  by  the  act  of  formation  of  the  soap — 
that  is,  the  union  of  the  alkali  with  the  fatty  acid — in  other  cases  by  the 
mechanical  shaking,  or  by  these  two  causes  combined.  The  application  of 
these  facts  to  the  action  of  the  pancreatic  juice  in  the  small  intestine  is 
easily  made.  When  the  chyme,  containing  more  or  less  of  liquid  fat,  comes 
into  contact  with  the  pancreatic  juice,  a  part  of  the  oil  is  quickly  split  by  the 
steapsin,  with  the  formation  of  free  fatty  acids.  These  acids  unite  with  the 
alkalies  and  the  alkaline  salts  present  in  the  secretions  of  the  small  intestine 
(pancreatic  juice,  bile,  intestinal  juice)  to  form  soaps.  The  formation  of  the 
soaps,  aided,  perhaps,  by  the  peristaltic  movements  of  the  intestine,  emulsifies 
the  remainder  of  the  fats  and  thus  prepares  them  for  absorption  or  further 
saponification.  It  has  been  suggested  that  the  proteids  in  solution  in  the 
pancreatic  juice  aid  in  the  emulsification,  but  there  is  no  experimental  evi- 
dence to  show  that  this  is  the  ease.  A  factor  of  much  more  Importance  is 
the  influence  of  the  bile.  In  man  the  pancreatic  juice  and  the  bile  are  poured 
into  the  duodenum  together,  and  in  all  mammals  the  two  secretions  are  mixed 
with  the  food  at  some  part  of  the  duodenum.  Now,  it  has  been  shown 
beyond  question  that  a  mixture  of  bile  and  pancreatic  juice  will  cause  a 
splitting  of  fats  into  fatty  acids  and  glycerin  much  more  rapidly  than  will  the 
pancreatic  juice  alone.1  This  effect  of  the  bile  is  not  due  to  the  presence  in 
it  of  a  fat-splitting  enzyme  of  its  own  :  the  bile  seems  merely  t"  favor  in 
some  way  the  action  of  the  steapsin  contained  in  the  pancreatic  secretion. 

1  Nencki :  Archiv  fiir  experimenfelU  Pathologic  ».  Pharmakologie,  1886,  Bd,  20,  S.  367;  Ratch- 
ford: Journal  of  Physiology,  1891,  vol.  12,  p.  27. 


308  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

Intestinal  Secretion. — The  small  intestine  is  lined  with  tubular  glands, 
the  crypts  of  Lieberkiihn,  that  are  supposed  to  form  a  secretion  of  consid- 
erable importance  in  digestion.  To  obtain  the  intestinal  secretion,  or  suceus 
enterims,  as  it  is  often  called,  recourse  lias  been  had  to  an  ingenious  operation 
for  establishing  a  permanent  intestinal  fistula.  This  operation,  which  usually 
goes  under  the  name  of  the  " Thhy-Vella  fistula,"  consists  in  cutting  out  a 
small  portion  of  the  intestine  without  injuring  its  supply  of  blood-vessels  or 
nerves,  and  then  sewing  the  two  open  ends  of  this  piece  into  the  abdominal 
wall  so  as  to  form  a  double  fistula.  The  continuity  of  the  intestines  is  estab- 
lished by  suture,  while  the  isolated  loop  with  its  two  openings  to  the  exterior 
can  lie  used  for  collecting  the  intestinal  secretion  uncontaminated  by  partially- 
digested  food.  The  secretion  is  always  small  in  quantity,  and  it  must  be 
started  by  a  stimulus  of  some  kind.  According  to  Rohmann,1  it  varies  in 
quantity  in  different  parts  of  the  small  intestine,  being  very  scanty  in  the  upper 
part  and  more  abundant  in  the  lower.  The  intestinal  secretion  is  a  yellowish 
liquid  with  a  strong  alkaline  reaction.  The  reaction  is  due  to  the  presence  of 
sodium  carbonate,  the  quantity  of  which  is  about  0.25  to  0.50  per  cent.  The 
chemical  composition  of  the  secretion  has  not  been  satisfactorily  determined, 
but  its  digestive  action  has  been  investigated  with  success.  Upon  proteids  and 
fats  it  is  said  to  have  no  specific  action — that  is,  it  contains  neither  a  proteolytic 
nor  a  fat-splitting  enzyme.  The  possible  value  of  its  sodium  carbonate  in  aiding 
the  emulsification  of  fats  has  been  referred  to  in  the  preceding  paragraph. 
Upon  carbohydrates  the  secretion  has  an  important  action.  In  the  first  place, 
it  has  been  shown  that  it  contains  an  amylolvtic  enzyme  that  is  more  abun- 
dant in  the  upper  than  in  the  lower  part  of  the  intestine.  This  enzyme  doubt- 
less aids  the  amylopsin  of  the  pancreatic  secretion  in  converting  starches  to 
sugar  (maltose)  or  sugar  and  dextrin.  What  is  still  more  important,  however, 
is  the  presence  of  inverting  enzymes  (invertase)  capable  of  converting  cane- 
sugar  (saccharose)  into  dextrose  and  levulose,  and  of  a  similar  enzyme  (mal- 
tase)  capable  of  changing  maltose  to  dextrose.  Both  of  these  effects  are 
examples   of  the    conversion    of  di-saccharides    to    niono-saecharides. 

The  di-saccharides  of  importance  in  digestion  are  cane-sugar,  milk-sugar, 
and  maltose.  The  first  of  these  forms  a  common  constituent  of  our  daily  diet; 
the  second  occurs  always  in  milk  ;  and  the  third,  as  we  have  seen,  is  the  main 
end-product  of  the  digestion  of  starches.  These  substances  are  all  readily 
Boluble,  and  we  might  expect  that  they  would  be  absorbed  directly  into  the 
blood  without  undergoing  further  change.  As  a  matter  of  fact,  however,  it 
seems  that  they  are  first  dissociated  under  the  influence  of  the  sugar-splitting 
enzymes  into  simpler  mono-saccharide  compounds,  although  in  the  case  of 
lactose  this  statement  is  perhaps  not  entirely  justified,  our  knowledge  of  the 
fate  of  this  sugar  during  absorption  being  as  yet  incomplete.  According 
to  some  authors,  lactose  is  absorbed  unchanged  (sec  Chemical  section), 
'flic  general  nature  of  this  change  is  expressed  in  the  three  following 
reaction-  : 

1  /'///(•/./■'.<  Arehiv  fur  die  gesammte  Physiologie,  1887,  l>d.  41,8.411. 


CHEMISTRY   OF  DIGESTION  AND   NUTRITION.  309 

C12T!„Ou  +  HaO  =  C6H1206  +  Cf>H1206. 

Maltose.  Dextrose.  Dextrose. 

C12H22Ou  +  H20  =  CfiH,A  +  C6H1206. 

Cane-sugar.  Dextrose..  Levulose. 

C12H22On  +  H20  =  C6H1206  +  06H12( ),, 

Lactose.  Dextrose.  Galactose. 

For  the  reactions  by  means  of  which  these  different  isomeric  forms  of  sugar  are 
distinguished  reference  must  be  made  to  the  Chemical  section.  The  final  stage 
in  the  artificial  digestion  of  starches  is  the  formation  of  maltose  or  of  a  mixture 
of  maltose  and  dextrins.  In  the  intestines,  however,  the  process  is  carried 
a  step  farther  by  the  aid  of  the  sugar-splitting  enzymes,  and  the  maltose,  and  ap- 
parently the  dextrins  also,  are  converted  into  dextrose.  According  to  this  descrip- 
tion, all  of  the  starch  is  finally  absorbed  into  the  blood  in  the  form  of  dextrose  ; 
and  this  conclusion  falls  in  with  the  fact  that  the  sugar  found  normally  in 
the  blood  exists  always  in  the  form  of  dextrose.  With  reference  to  the 
sugar-splitting  enzymes  found  in  the  small  intestine,  it  should  be  added  that 
they  occur  more  abundantly  in  the  mucous  membrane  than  in  the  secretion 
itself.  Indeed,  the  secretion  is  normally  so  scanty,  especially  in  the  upper 
part  of  the  intestine,  that  it  cannot  be  supposed  to  do  more  than  moisten  the 
free  surface,  and  it  is  probable  that  the  action  of  these  enzymes  takes  place 
upon  or  in  the  mucous  membrane,  as  the  last  step  in  the  series  of  digestive 
changes  of  the  carbohydrates  immediately  preceding  their  absorption. 

Digestion  in  the  Large  Intestine. — Observations  upon  the  secretions  of 
the  large  intestine  have  been  made  upon  human  beings  in  cases  of  anus  praeter- 
naturalis in  which  the  lower  portion  of  the  intestine  (rectum)  was  practically 
isolated.  These  observations,  together  with  those  made  upon  lower  animals, 
unite  in  showing  that  the  secretion  of  the  large  intestine  is  mainly  composed 
of  mucus,  as  the  histology  of  the  mucous  membrane  would  indicate,  and  that 
it  is  very  alkaline,  and  probably  contains  no  digestive  enzymes  of  its  own. 
When  the  contents  of  the  small  intestine  pass  through  the  ileo-csecal  valve  into 
the  colon  they  still  contain  a  quantity  of  incompletely  digested  material  mixed 
with  the  enzymes  of  the  small  intestine.  It  is  likely,  therefore,  that  seme 
at  least  of  the  digestive  processes  described  above  may  keep  on  for  a  time  in 
the  large  intestine;  but  the  changes  hereof  most  interest  are  the  absorption 
that  takes  place  and  the  bacterial  decompositions.  The  latter  arc  described 
briefly  below. 

Bacterial  Decompositions  in  the  Intestines. —  Bacteria  of  different 
kinds  have  been  found  throughout  the  alimentary  canal  from  the  mouth  t<> 
the  rectum.  In  the  stomach,  however,  under  normal  conditions,  the  strong 
acid  reaction  prevents  the  action  of  those  putrefactive  bacteria  that  decom- 
pose proteids,  and  prevents  or  greatly  retards  the  action  of  those  thai  set  up 
fermentation  in  the  carbohydrates.  Under  certain  abnormal  conditions 
known  to  ns  under  the  general  term  of  dyspepsia,  bacterial  fermentation  of 
the  carbohydrates  may  be  pronounced,  l>nt  this  must  be  considered  as  path- 
ological. 


310  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

In  the  small  intestine  the  secretions  are  all  alkaline,  and  it  was  formerly 
taken  for  granted  that  the  intestinal  contents  an'  normally  alkaline,  [fthis  were 
so,  the  bacteria  would  find  a  favorable  environment.  It  was  supposed  that 
putrefaction  of  the  proteids  mighl  occur,  especially  during  the  act  of  tryptic 
digestion,  and  this  supposition  was  home  out  by  the  extraordinary  readiness  of  ar- 
tificial pancreatic  digestions  to  undergo  putrefaction  when  not  protected  in  some 
way.  Two  recent  cases  '  of  fistula  of  the  ileum  at  its  junction  with  the  colon  in 
human  beings  have  given  opportunity  for  exact  study  of  the  contents  of  the 
small  intestine.  The  results  are  interesting,  and  to  a  certain  extent  are  opposed 
to  the  preconceived  notions  as  to  reaction  and  proteid  putrefaction  which  have 
just  been  stated.  They  show  that  the  contents  of  the  intestine  at  the  point 
where  they  are  about  to  pass  into  the  large  intestine  are  acid,  provided  a  mixed 
diet  is  used,  the  acidity  being  due  to  organic  acids  (aeetie)  and  being  equal  to 
0.1  per  cent,  acetic  acid.  These  acids  must  have  come  from  the  bacterial  fer- 
mentation of  the  carbohydrates,  and  a  number  of  bacteria  capable  of  producing 
such  fermentation  were  isolated.  The  products  of  bacterial  putrefaction  of  the 
proteids.  on  the  contrary,  were  absent,  and  it  has  been  suggested  that  the  acid 
reaction  produced  by  the  fermentation  of  the  carbohydrates  serves  the  useful 
purpose,  under  normal  conditions,  of  preventing  the  putrefaction  of  the  pro- 
teids. With  reference,  therefore,  to  the  point  we  are  discussing — namely,  the 
bacterial  decomposition  of  the  contents  of  the  intestines — we  may  conclude, 
upon  the  evidence  furnished  by  these  two  cases,  that  in  the  human  being,  when 
living  on  a  mixed  diet,  some  of  the  carbohydrates  undergo  bacterial  decompo- 
sition in  the  small  intestine,  but  that  the  proteids  are  protected.  We  may 
further  suppose  that  in  the  case  of  the  proteids  the  limits  of  protection  are 
easilv  overstepped,  and  that  such  a  condition  as  a  large  excess  of  proteid  in  the 
diet  or  a  deficient  absorption  from  the  small  intestine  may  easily  lead  to  exten- 
sive intestinal  putrefaction  involving  the  proteids  as  well  as  the  carbohydrates. 

In  the  large  intestine,  on  the  contrary,  the  alkaline  reaction  of  the  secretion 
is  more  than  sufficient  to  neutralize  the  organic  acids  arising  from  fermentation 
of  the  carbohydrates,  and  the  reaction  of  the  contents  is  therefore  alkaline. 
Here,  then,  what  remains  of  the  proteids  undergoes,  or  may  undergo,  putrefac- 
tion, and  this  process  must  be  looked  upon  as  a  normal  occurrence  in  the  large 
intestine.  The  extent  of  the  bacterial  action  upon  the  proteids  as  well  as  the 
carbohydrates  may  vary  widely  even  within  the  limits  of  health,  and  if  excessive 
may  lead  to  intestinal  troubles.  Among  the  products  formed  in  this  way,  the 
following  are  known  to  occur:  Leucin,  tyrosin,  and  other  amido-acids ;  indol ; 
skatol ;  phenols;  various  members  of  the  fatty-acid  series,  such  as  lactic, 
butyric,  and  caproic  acids;  sulphuretted  hydrogen;  methane;  hydrogen; 
methyl  mercaptan,  etc.  Some  of  these  products  will  be  described  more  fully 
in  treating  of  the  composition  of  the  feces.  To  what  extent  these  products 
are  of  value  to  the  body  it  is  difficult,  with  our  imperfect  knowledge,  to  say. 
It  ha-   been  pointed  out,  on  the  one  hand,  that  some  of  them  (skatol,  fatty 

1  Macfayden,  Ncncki,  and  Sieber:  Archivfur  experimentelle  Pathologie  u.  Pharmakologie,  1891' 
Bd.  'J-1,  S.  311  ;  Jakowski :  Archives  des  Sciences  biologiques,  St.  Petersburg,  1892,  t.  1. 


CHEMISTRY   OF  DIGESTION   AND   NUTRITION.  311 

acids,  CO,,  CH4,  and  H2S)  promote  the  movements  of  the  intestine,  and  may 
be  of  value  from  this  standpoint;  on  the  other  hand,  some  of  them  are 
absorbed  into  the  blood,  to  be  eliminated  again  in  different  form  in  the  urine 
(indol  aud  phenols),  and  it  may  be  that  they  are  of  importance  in  the  metab- 
olism of  the  body;  but  concerning  this  our  knowledge  is  deficient.  On  the 
whole,  we  must  believe  that  the  food  in  its  passage  through  the  alimentary 
canal  is  acted  upon  mainly  by  the  digestive  enzymes,  the  so-called  "  unorgan- 
ized" ferments,  but  that  the  action  of  the  bacteria,  or  organized  ferment-,  is 
responsible  for  a  part  of  the  changes  that  the  food  undergoes  before  its  final 
elimination  in  the  form  of  feces.  These  two  kinds  of  action  vary  greatly 
within  normal  limits,  and  to  a  certain  extent  they  seem  to  be  in  inverse 
relationship  to  each  other.  When  the  digestive  enzymes  and  secretion-  are 
deficient  or  ineifective  the  field  of  action  for  the  bacteria  is  increased,  and  this 
seems  to  be  the  case  in  some  pathological  conditions,  the  result  being  intes- 
tinal troubles  of  various  kinds.  The  limits  of  normal  bacterial  action  have 
not  been  worked  out  satisfactorily,  but  it  is  evident  that  our  knowledge  <>f 
digestion  will  not  be  complete  until  this  is  accomplished. 

It  should  be  stated  in  conclusion  that,  however  constant  and  important 
the  occurrence  of  bacterial  fermentation  may  be  in  the  alimentary  canal,  it 
cannot  be  regarded  as  essential  to  the  life  of  the  animal,  since  Nuttall  and 
Theirfelder,1  in  a  series  of  ingenious  experiments  made  upon  newly-born 
guinea-pigs,  have  shown  that  these  animals  may  thrive,  for  a  time  at  least, 
when  the  entire  alimentary  canal   is  free  from  bacteria. 

E.  Absorption  ;    Summary  of  Digestion  and   Absorption   of 
the  Food-stuffs  ;  Feces. 

In  the  preceding  sections  we  have  followed  the  action  of  the  various 
digestive  secretions  upon  the  food-stuifs  as  far  as  the  formation  of  the  supposed 
end-products.  In  order  that  these  products  may  be  of  actual  nutritive  value 
to  the  body,  it  is  necessary,  of  course,  that  they  shall  be  absorbed  into  the 
circulation  and  thus  be  distributed  to  the  tissues.  There  are  two  possible 
routes  for  the  absorbed  products  to  take:  they  may  pass  immediately  into  the 
blood,  or  they  may  enter  the  lymphatic  system,  the  so-called  "lacteals"  of 
the  alimentary  canal.  In  the  latter  case  they  reach  the  blood  finally  before 
being  distributed  to  the  tissues,  since  the  thoracic  duct,  into  which  the  lym- 
phatics of  the  alimentary  canal  all  empty,  opens  into  the  blood-vascular  system 
at  the  junction  of  the  left  internal  jugular  and  subclavian  veins.  The  sub- 
stances that  take  this  route  are  distributed  to  the  tissues  by  the  blood,  but 
it  is  to  be  noticed  that,  owing  to  the  sluggish  How  of  the  lymph-circulation 
(see  section  on  Circulation),  a  relatively  long  time  elapses  after  digestion 
.  before  they  enter  the  blood-current.  The  products  that  enter  the  blood 
directly  from  the  alimentary  canal  are  distributed  rapidly  ;  but  in  this  case  we 
must  remember  that  they  first  pass  through  the  liver,  owing  to  the  existence  of 
1  Zeittschriflfiir  phyaiologische  Ohemie,  18'.)-"),  lid.  >J1  ;   1896,  Bd.  22,  ami  L897,  Bd.  23. 


312  AN   AMERICAN   TEXT- BOOK   OF  PHYSIOLOGY. 

the  portal  circulation,  before  they  reach  the  general  circulation.  During  this 
passage  through  the  liver,  as  we  shall  find,  changes  of  the  greatest  importance 
take  place.  The  physiology  of  absorption  is  concerned  with  the  physical  and 
chemical  means  by  which  the  end-products  of  digestion  are  taken  up  bv  the 
blood  or  the  lymph,  and  the  relative  importance  of  the  stomach,  the  small 
intestine,  and  the  large  intestine  in  this  process.  Leaving  aside  the  fats, 
whose  absorption  is  a  special  case,  the  absorption  of  the  other  products  of 
digestion  was  formerly  thought  to  be  a  simple  physical  process.  The  processes 
of  diffusion  and  osmosis,  as  they  are  known  to  occur  outside  the  body,  were 
supposed  to  account  for  the  absorption  of  all  the  soluble  products.  This 
belief  is  still  held  by  many,  hut  the  facts  known  with  regard  to  the  absorp- 
tion of  the  carbohydrates,  proteids,  and  fats  after  the  changes  undergone 
during  digestion  are  not  wholly  accounted  for  by  the  laws  of  diffusion  and 
osmosis  as  they  are  known  to  us  (see  p.  65  for  a  discussion  of  the  nature  of 
these  processes).  For  the  present  at  least  it  seems  to  be  necessary  to  refer 
many  of  the  phenomena  of  physiological  absorption  to  the  peculiar  properties 
of  the  living  epithelial  cells  lining  the  alimentary  canal.  Some  of  the 
important  facts  regarding  absorption  are  as  follows  : 

Absorption  in  the  Stomach. — In  the  stomach  it  is  possible  that  there 
might  be  absorption  of  the  following  substances :  water;  salts;  sugars  and 
dextrins  that  may  have  been  formed  in  salivary  digestion  from  starch,  or 
that  may  have  been  eaten  as  such  ;  the  proteoses  and  peptones  formed  in 
the  peptic  digestion  of  proteids  or  albuminoids.  In  addition,  absorption  of 
soluble  or  liquid  substances — drugs,  alcohol,  etc. — that  have  been  swallowed 
may  occur.  It  was  formerly  assumed  without  definite  proof  that  the  absorp- 
tion in  the  stomach  of  such  things  as  water,  salts,  sugars,  and  peptones  was 
very  important.  Of  late  years  a  number  of  actual  experiments  have  been 
made,  under  conditions  as  nearly  normal  as  possible,  to  determine  the  extent 
of  absorption  in  this  organ.  These  experiments  have  given  unexpected  results, 
showing,  upon  the  whole,  that  absorption  does  not  take  place  readily  in  the 
stomach — certainly  nothing  like  so  easily  as  in  the  intestine.  The  methods 
made  use  of  in  these  experiments  have  varied,  but  the  most  interesting  results 
have  been  obtained  by  establishing  a  fistula  of  the  duodenum  just  beyond  the 
pylorus.1  Through  a  fistula  in  this  position  substances  cau  be  introduced  into 
the  stomach,  and  if  the  cardiac  orifice  is  at  the  same  time  shut  off  by  a  ligature 
or  a  small  balloon,  they  can  be  kept  in  the  stomach  a  given  time,  then  be 
removed,  and  the  changes,  if  any,  be  noted.  After  establishing  the  fistula  in 
the  duodenum  food  may  be  given  to  the  animal,  and  the  contents  of  the 
stomach  as  they  pass  out  through  the  fistula  may  be  caught  and  examined. 
The  older  methods  of  introducing  the  substance  to  be  observed  into  the 
stomach  through  the  oesophagus  or  through  a  gastric  fistula  were  of  little  use, 
since,  if  the  substance  disappeared,  there  was  no  way  of  deciding  whether  it 
was  absorbed  or  was  -imply   passed   on   into  the  intestine. 

1  (  lompare  von  Mering:  Verhandl.  </<:<  Congresses  f.  innere  Med.,  12,  471,  189.'?;  Edkins: 
Journal  of  Physiology,  1892,  vol.  13,  p.  44".;  Brandl:  Zeii&chrift  fur  Biologie,  1892,  Bd.  29, 
8.  277. 


CHEMISTRY  OF  DIGESTION  AND  NUTRITION.  313 

Water. — Experiments  of  the  character  just  described  show  that  water  when 
taken  alone  is  practically  not  absorbed  at  all  in  the  stomach.  Von  Mering's 
experiments  especially  show  that  as  soon  as  water  is  introduced  into  the 
stomach  it  begins  to  pass  out  into  the  intestine,  being  forced  out  in  a  series 
of  spirts  by  the  contractions  of  the  stomach.  Within  a  comparatively  short 
time  practically  all  the  water  can  be  recovered  in  this  way,  none  or  very  little 
having  been  absorbed  in  the  stomach.  For  example,  in  a  large  dog  with  a 
fistula  in  the  duodenum,  500  cubic  centimeters  of  water  were  given  through 
the  mouth.  Within  twenty-five  minutes  495  cubic  centimeters  had  been 
forced  out  of  the  stomach  through  the  duodenal  fistula.  The  result  was  not 
true  for  all  liquids  ;  alcohol,  for  example,  was  absorbed  readily. 

Salts. — The  absorption  of  salts  from  the  stomach  has  not  been  investigated 
thoroughlv.  According  to  Brandl,  sodium  iodide  is  absorbed  very  slowly  or 
not  at  all  in  dilute  solutions.  Not  until  its  solutions  reach  a  concentration  of 
3  per  cent,  or  more  does  its  absorption  become  important.  This  result,  if 
applicable  to  all  the  soluble  inorganic  salts,  would  indicate  that  under  ordi- 
nary conditions  they  are  practically  not  absorbed  in  the  stomach,  since  it  can- 
not be  supposed  that  they  are  normally  swallowed  in  solutions  so  concentrated 
as  3  per  cent.  It  was  found  that  the  absorption  of  sodium  iodide  was  very 
much  facilitated  by  the  use  of  condiments,  such  as  mustard  and  pepper,  or 
alcohol,  which  act  either  by  causing  a  greater  congestion  of  the  mucous  mem- 
brane or  perhaps  by  directly  stimulating  the  epithelial  cells. 

Sugars  and  Peptones. — Experiments  by  the  newer  methods  leave  no  doubt 
that  sugars  and  peptones  can  be  absorbed  from  the  stomach.  In  Yon  Mering's 
work  different  forms  of  sugar — dextrose,  lactose,  saccharose  (cane-sugar),  maltose, 
and  also  dextrin — were  tested.  They  were  all  absorbed,  but  it  was  found 
that  absorption  was  more  marked  the  more  concentrated  were  the  solutions. 
Brandl,  however,  reports  that  sugar  (dextrose)  and  peptone  were  not  sensibly 
absorbed  until  the  concentration  had  reached  5  per  cent.  With  these  -(di- 
stances also  the  ingestion  of  condiments  or  of  alcohol  increased  distinctly  the 
absorptive  processe-  in  the  stomach.  On  the  whole  it  would  seem  that  sugars 
and  peptones  are  absorbed  with  some  difficulty  from  the  stomach. 

Fats. — As  we  have  seen,  fats  undergo  no  digestive  changes  in  the  stomach. 
The  processes  of  saponification  and  emulsification  are  supposed  to  be  pre- 
liminary steps  to  absorption,  and,  as  these  processes  take  place  only  after 
the  fats  have  reached  the  small  intestine,  there  seems  to  be  no  doubt  that  in 
the  stomach  fats  escape  absorption  entirely. 

Absorption  in  the  Small  Intestine. — The  soluble  products  of  digestion — 
sugars  and  peptones  or  proteoses,  as  well  as  the  saponified  and  emulsified 
fats — are  mainly  absorbed  in  the  small  intestine.  This  we  should  ex- 
pect from  ;i  mere  <i  priori  consideration  of  the  conditions  prevailing  in 
this  part  of  the  alimentary  canal.  The  partially-digested  food  sent  out 
from  the  stomach  meets  the  digestive  secretions  in  the  beginning  of 
the  small  intestine.  As  we  have  seen,  the  different  enzymes  of  the  pan- 
creatic secretion  act  powerfully  upon  the  three  important  classes  of  food- 
stuffs,  and    we    have   every    reason    to    believe    that    their    digestion    make- 


314  AN   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

rapid  progress.  The  passage  of  the  food  along  the  small  intestine,  although 
rapid  compared  with  its  passage  through  the  large  intestine,  requires  a 
number  of  hours  for  its  completion.  According  to  the  observations  made 
upon  a  patient  with  a  fistula  at  the  end  of  the  small  intestine,1  food  begins  to 
pass  into  the  large  intestine  in  from  two  to  five  and  a  quarter  hours  after  it 
has  been  eaten,  and  it  requires  from  nine  to  twenty-three  hours  before  the  last 
portions  reach  the  end  of  the  small  intestine;  this  estimate  includes, of  course, 
the  time  in  the  stomach.  During  this  progress  it  has  been  converted  for  the 
most  part  into  a  condition  suitable  for  absorption,  and  the  mucous  membrane 
with  which  it  is  in  contact  is  one  peculiarly  adapted  for  absorption,  since  its 
epithelial  surface  is  greatly  increased  in  extent  by  the  vast  number  of  villi 
as  well  as  by  the  numerous  large  folds  known  as  the  "  valvula?  conniventes." 
In  addition  to  these  considerations,  however,  we  have  abundant  experimental 
proof  that  absorption  takes  place  actively  in  the  small  intestine.  The  absorp- 
tion of  fats  can  be  demonstrated  microscopically,  as  will  be  described  presently. 
Experiments  made  by  Eohmann 2  and  others  with  isolated  loops  of  intestine 
have  shown  that  sugars  and  peptones  are  absorbed  readily  and  in  much  more 
dilute  solutions  than  in  the  stomach.  Moreover,  in  the  case  just  referred  to, 
of  an  intestinal  fistula  at  the  end  of  the  small  intestine,  a  determination  of 
the  proteid  present  in  the  discharge  from  the  fistula,  after  a  test-meal  contain- 
ing a  known  amount  of  proteid,  showed  that  about  85  per  cent,  had  disappeared 
— that  is,  had  been  absorbed  before  reaching  the  large  intestine.  With  refer- 
ence to  water  and  salts,  it  has  been  shown  that  they  also  are  readily  absorbed  ; 
some  very  interesting  experiments  demonstrating  this  fact  have  been  reported 
by  Heidenhain.3  it  must  be  remembered,  however,  that  under  normal  con- 
ditions the  absorption  of  water  and  salts  is  more  or  less  compensated  by  the 
secretion  formed  along  the  length  of  the  intestine,  so  that  when  the  contents 
reach  the  ileo-caecal  valve  they  are  still  of  a  fluid  consistency  similar  to  that 
of  the  chyme  when  it  left  the  stomach  to  enter  the  intestine.  A  consideration 
of  the  mechanism  of  the  absorption  of  fats,  sugars,  peptones,  and  water  will 
be  taken  up  presently,  after  a  few  words  have  been  said  of  absorption  in  the 
large  intestine. 

Absorption  in  the  Large  Intestine. — There  can  be  no  doubt  that  absorp- 
tion forms  an  important  part  of  the  function  of  the  large  intestine.  The 
contents  pass  through  it  with  great  slowness,  the  average  duration  being  given 
usually  as  twelve  hours,  and  while  they  enter  through  the  ileo-caecal  valve  in  a 
thin  fluid  condition,  they  leave  the  rectum  in  the  form  of*  nearly  solid  feces. 
This  fact  alone  demonstrates  the  extent  of  the  absorption  of  water.  As  for 
the  sugar  and  peptones,  examination  of  the  intestinal  contents  as  they  entered 
the  large  intestine  in  the  case  of  fistula  cited  in  the  preceding  paragraph 
showed  that  there  may  still  be  present  an  important  percentage  of  proteid 
(14    per   cent.)   and    a   variable    amount    of  sugars    and    fats — more    than    is 

1  Macfadyen,  Nencki,  and  Sieber :  Archiv  filr  experimentelle  Pathologie  u.  Pharmakolorjie,  1891, 
Bd.  28,  S.  311. 

3  Pjliiger's  Archiv  fur  die  gesammte  Physiologic,  1887,  Bd.  41,  S.  411. 
J  find.,  1894,  Bd.  oti,  S.  637. 


CHEMISTRY   OF  DIGESTION  AXD    NUTRITION.  315 

found  normally  in  the  feces.  Some  of  this  carbohydrate  and  proteid  under- 
goes destruction  by  bacterial  action,  as  has  already  been  explained  (p.  310), 
but  some  of  it  is  absorbed,  or  may  be  absorbed,  before  decomposition  occurs. 
The  power  of  absorption  in  the  large  intestine  has  been  strikingly  demon- 
strated by  the  fact  that  various  substances  injected  into  the  rectum  are 
absorbed  and  suffice  to  nourish  the  animal.  Enemata  of  this  character  are 
frequently  used  in  medical  practice  with  satisfactory  results,  and  careful 
experimental  work  on  lower  animals  and  on  men  under  conditions  capable  of 
being  properly  controlled  has  corroborated  the  results  of  medical  experience 
and  shown  that  even  in  the  rectum  absorption  takes  place.  Without  giving 
the  details  of  this  work,  it  may  be  said  that  it  is  now  known  that  proteids  in 
solution,  or  even  such  things  as  eggs  beaten  to  a  fluid  mass  with  a  little  salt, 
are  absorbed  from  the  rectum,  and  this  notwithstanding  the  fact  that  no 
proteolytic  enzyme  is  found  in  this  part  of  the  alimentary  canal.  Fats  also 
(such  as  milk-fat)  and  sugars  can  be  absorbed  in  the  same  way.  Some  of 
these  facts  have  been  corroborated  in  a  striking  way  by  Harley  '  in  experi- 
ments upon  dogs  from  which  he  had  removed  the  whole  of  the  large  intes- 
tine. It  was  found  that  in  these  animals  there  was  an  increase  in  the  quan- 
tity of  water  in  the  feces,  the  total  quantity  being  nearly  five  times  as  much 
as  in  the  normal  dog. 

Absorption  of  Proteids. — As  we  have  seen  in  the  preceding  paragraphs, 
absorption  of  proteids  takes  place  in  the  stomach  and  the  small  and  large 
intestines,  but  in  all  probability  mainly  in  the  small  intestine.  The  end- 
products  of  the  digestion  of  proteids  by  the  proteolytic  enzymes  are  proteoses 
and  peptones.  Tryptic  digestion  produces  also  leucin,  tyrosin,  and  the  related 
amido-  bodies,  but  so  far  as  proteid  has  undergone  decomposition  to  this  stage 
it  is  no  longer  proteid,  and  does  not  have  the  nutritive  value  of  proteid.  The 
logical  conclusion  from  our  knowledge  of  proteid  digestion  should  be  that 
all  proteid  is  reduced  to  the  form  of  proteoses  or  peptones  before  absorption, 
and  that  the  great  advantage  of  proteolysis  is  that  proteids  are  more  readily 
absorbed  in  this  form  than  in  any  other.  In  the  main  we  must  accept  this 
conclusion.  The  process  of  proteid  digestion  would  seem  to  be  without  mean- 
ing otherwise.  But  we  must  not  shut  our  eyes  to  the  fact  that  proteid  may  be 
absorbed  in  other  forms  than  peptones  or  proteoses.  This  has  been  demon- 
strated most  clearly  for  the  rectum  and  the  lower  part  of  the  colon,  as  was 
stated  in  the  preceding  paragraph.  Enemata  of  dissolved  muscle-proteid 
(myosin),  egg-albumin,  etc.  are  absorbed  from  this  part  of  the  alimentary  canal 
without,  so  far  as  can  be  determined,  previous  conversion  to  peptones  and 
proteoses,  and  we  must  admit  that  the  same  power  is  possessed  by  other 
parts  of  the  intestinal  tract.  It  is  probable,  for  instance,  that  the  very  first 
product  of  pepsin-hydrochloric  digestion,  syntonin,  is  capable  of  absorption 
directly.  This  fact,  however,  does  not  weaken  the  conclusion  thai  peptones 
and  proteoses  are  absorbed  more  easily  than  other  forms  of  proteids,  and  that 
they  constitute  the  form  in  which  the  bulk  of  our  proteid  is  absorbed. 
1  "Proceedings  of  /In-  Royal  Society,  London,  L899,  vol.  Ixiv.  No.  408. 


31(3  AN   AMERICAN    TEXT- HOOK    OE   PHYSIOLOGY. 

Opinion-  as  to  why  these  forms  of  proteids  are  more  easily  absorbed  than  any 

other  must  vary  with  the  theory  held  as  to  the  nature  of  absorption.  Ex- 
periments have  shown  thai  proteoses  and  peptones  are  more  easily  diffusible 
than  other  forms  of  proteids,  and  this  Pact  tends  to  support  the  view  that 
their  absorption  is  due  to  physical  diffusion.  The  object  of  digestion,  on  this 
view,  is  to  convert  the  insoluble  and  non-dialyzable  proteids  into  soluble, 
diffusible  peptones.  But  a  study  of  the  details  of  proteid  absorption  has 
shown  that  the  process  cannot  be  explained  entirely  by  the  laws  of  simple 
dialysis  that  govern  the  process  <>f  diffusion  through  dead  membranes.  Pro- 
teids, like  egg-albumin,  which  are  practically  non-dialyzable  are  absorbed 
readily  from  the  intestine.  Moreover,  when  one  considers  the  rate  of  absorp- 
tion of  peptone  from  the  alimentary  tract,  it  seems  to  be  much  too  rapid  and 
complete  to  be  accounted  for  entirely  by  the  diffusibility  of  this  substance  as 
determined  by  experiments  with  parchment  dialyzers.  It  is  believed,  there- 
fore, that  the  initial  act  in  the  absorption  of  proteids  is  dependent  in  some 
way  upon  the  peculiar  properties  of  the  layer  of  living  epithelial  cells  lining 
the  mucous  membrane.  Whether  the  peculiarity  is  a  physical  one  depending 
on  some  special  structure  of  the  cells  that  makes  them  permeable  to  the  pro- 
teid molecules,  or  whether  it  is  a  more  obscure  and  complicated  process  con- 
nected with  the  living  activity  of  the  cells,  remains  undetermined  for  the 
present.  After  the  proteids  have  passed  through  the  epithelium  it  is  a 
matter  of  importance  to  determine  whether  they  enter  the  blood  or  the 
lymph  circulation.  Experiments  have  shown  conclusively  that  they  are 
transmitted  directly  to  the  blood-capillaries:  ligature  of  the  thoracic  duct, 
for  example,  which  shuts  oil'  the  entire  lymph-How  coming  from  the  intes- 
tine, does  not  interfere  with  the  absorption  of  proteids.  There  is  one  other 
fact  of  great  significance  in  connection  with  this  subject:  the  proteids  are 
absorbed  mainly,  if  not  entirely,  as  proteoses  and  peptones,  and  they  pass 
immediately  into  the  blood  ;  nevertheless,  examination  of  the  blood  directly 
after  eating,  while  the  process  of  absorption  is  in  full  activity,  fails  to  show 
any  peptones  or  proteoses  in  the  blood.  In  fact,  if  these  substances  are 
injected  directly  into  the  blood,  they  behave  as  foreign,  and  even  as  toxic, 
bodies.  In  certain  doses  they  produce  insensibility  with  lowered  blood- 
pressure,  and  they  may  bring  on  a  condition  of  coma  ending  in  death. 
Moreover,  when  present  in  the  blood,  even  in  small  quantities,  they  are 
eliminated  by  the  kidneys  and  are  evidently  unfit  for  the  use  of  the  tissues. 
It  follows  from  these  facts  that  while  the  peptones  and  proteoses  arc  being 
absorbed  by  the  epithelial  cells  they  arc  at  the  same  time  changed  into  some 
other  form  of  proteid.  YVhal  this  change  is  has  not  been  determined.  Ex- 
periments have  Bhown  thai  peptones  disappear  when  brought  into  contact 
with  fresh  pieces  of  the  lining  mucous  membrane  of  the  intestine  which  are 
-till  in  a  living  condition.  The  statement  has  been  made  that  the  peptones 
and  proteoses  are  converted  to  serum-albumin,  or  at  least  to  a  native  albumin 
of  some  kind,  but  we  have  no  definite  knowledge  beyond  the  fact  that  the 
peptones  and  proteoses,  a-  such,  disappear.     It  is  well  to  call  attention  to  the 


CHEMISTRY  OF  DIGESTION   AND   NUTRITION.  :U7 

fact  that  the  digestion  of  proteids  is  supposed,  according  to  the  schema  already 
described,  to  consist  in  a  process  of  hydration  and  splitting,  with  the  forma- 
tion, probably,  of  smaller  molecules.  The  reverse  act  of  conversion  of  pep- 
tones hack  to  albumin  implies,  therefore,  a  process  of  dehydration  and  poly- 
merization that  presumably  takes  place  in  the  epithelial  cells.  It  is  at  this 
point  in  the  act  of  absorption  of  proteids  that  our  knowledge  ismosl  deficient. 

Absorption  of  Sugars.— The  carbohydrates  are  absorbed  mainly  in  the 
form  of  sugar  or  of  sugar  and  dextrin.  Starches  are  converted  in  the  intes- 
tine into  maltose  or  maltose  and  dextrin,  and  then  by  the  sugar-splitting 
enzymes  of  the  mucous  membrane  are  changed  to  dextrose.  Ordinary  cane- 
sugar  is  hydrolyzed  into  dextrose  and  levulose  before  absorption,  and  milk- 
sugar  possibly  undergoes  a  similar  change  to  dextrose  and  galactose,  though 
less  is  known  of  this.  So  far  as  our  knowledge  goes,  then,  we  may  say  that 
the  carbohydrates  of  our  food  are  eventually  absorbed  in  the  form  mainly  of 
dextrose  or  of  dextrose  and  levulose,  leaving  out  of  consideration,  of  course, 
the  small  part  that  normally  undergoes  bacterial  fermentation.  In  accordance 
with  this  statement,  we  find  that  the  sugar  of  the  blood  exists  in  the  form 
of  dextrose.  It  is  apparently  a  form  of  sugar  that  can  be  oxidized  very 
readily  by  the  tissues.  In  fact,  it  has  been  shown  that  if  cane-sugar  is  in- 
jected directly  into  the  blood,  it  cannot  be  utilized,  at  least  not  readily,  by 
the  tissues,  since  it  is  eliminated  in  the  urine;  whereas  if  dextrose  is  intro- 
duced directly  into  the  circulation,  it  is  all  consumed,  provided  it  is  not 
injected  too  rapidly.  The  sugars  are  soluble  and  dialyzable,  but,  as  in  the 
cn*r  of  peptones,  exact  study  of  their  absorption  shows  that  it  does  not  fellow 
in  detail  the  known  laws  of  osmosis  through  dead  membranes.  Experiments 
indicate,  however,  that  in  a  general  way  the  behavior  of  solutions  of  sugar 
placed  in  isolated  loops  of  the  intestine  may  be  understood  by  assuming  that 
a  diffusion  takes  place, and  it  may  be  therefore  that  the  peculiarities  observed 
are  connected  with  the  structure  of  the  living  epithelium.  We  have  to  deal 
here,  in  fact,  with  the  same  difficulty  as  was  encountered  in  the  case  of  the 
proteids.  A  special  vital  activity  of  the  epithelial  cells  ciinnot  be  excluded, 
and  we  must  be  content  to  await  a  fuller  development  of  experimental  inves- 
tigation before  attempting  to  come  to  a  final  conclusion.  As  in  the  case  of 
the  proteids,  the  absorbed  sugars — dextrose  or  dextrose  and  levulose — pass 
directly  into  the  blood,  and  do  not  under  normal  conditions  enter  the  lymph- 
vessels.  This  has  been  demonstrated  by  direct  examination  of  the  blood  of 
the  portal  vein  during  digestion  (von  Mering1),  a  distinct  increase  in  its 
sugar-contents  being  found.  Examination  of  the  lvmph  shows  no  increase  in 
sugar  unless  excessive  amounts  of  carbohydrates  have  been  eaten  (Ileiden- 
hain). 

Absorption   of  Fats. — As   has   been    stated,  fats   are   absorbed    either   in 
solid  form,  as  emulsified   droplets,  or  as  fatty  acids  or  soaps.      In  the    latter 
case   the    fatty  acids   are   again    recombined    tit    particles   of   neutral    fat,  pre- 
sumably within  the  substance  of  the  epithelial  cells.    So  far  as  the  emulsified  fat 
1  Dn  Bois-Reymond's  Archivfur  Analomit  uml  Physiologie,  1^77,  S.  II.",. 


318  AN    AMERICAN    TEXT- HOOK    OF    PHYSIOLOGY. 

i-  concerned,  the  process  of  absorption  must  be  of  a  mechanical  nature.  The 
details  of  the  process  have  been  worked  ouf  microscopically  and  have  given 
rise  to  numerous  researches.  It  is  unnecessary  to  speak  of  the  various 
theories  that  have  been  held,  as  it  has  been  shown  by  nearly  all  the  recent 
work  that  the  immediate  agent  in  the  absorption  of  fats  is  again  the  epi- 
thelial cells  of  the  villi  of  the  small  intestine.  The  fat-droplets  may  be 
seen  within  these  cells,  and  can  be  studied  microscopically  alter  digestion 
in  the  act  of  passing,  or  rather  of  being  passed,  through  the  cell-substance. 
Reference  to  the  histology  of  the  villi  will  show  that  each  villus  possesses 
a  comparatively  large  lymphatic  capillary  lying  in  its  middle  and  ending 
blindly,  apparently,  near  the  apex  of  the  villus.  Between  this  central  lym- 
phatic— or  lacteal,  as  it  is  called  here — and  the  epithelium  lies  the  stroma,  or 
main  substance  of  the  villus,  which,  in  addition  to  its  blood-capillaries  and 
plain  muscle-fibres,  consists  mainly  of  lymphoid  or  adenoid  tissue  containing 
numerous  leucocytes.  The  fat-droplets  have  to  pass  from  the  epithelium  to 
the  central  lymphatic,  for  it  is  one  of  the  most  certain  facts  in  absorption,  and 
one  which  has  been  long  known,  that  the  fat  absorbed  gets  eventually  into 
the  iacteals  in  an  emulsified  condition  and  thence  is  conveyed  through  the 
svstem  of  lymphatic  vessels  to  the  thoracic  duct  and  finally  to  the  blood. 
The  name  "  lacteal,"  in  fact,  is  given  to  the  lymphatic  capillaries  of  the  villus 
on  account  of  the  milky  appearance  of  their  contents,  after  meals,  caused  by 
the  emulsified  fat.  It  should  be  added,  however,  that  it  has  not  been  possible 
to  demonstrate  experimentally  that  all  the  absorbed  fat  passes  into  the  thoracic 
duct.  Attempts  have  been  made  to  collect  all  the  fat  passing  through  the 
thoracic  duct  after  a  meal  containing  a  known  quantity  of  fat,  but  even  after 
making  allowance  for  the  unabsorbed  fat  in  the  feces  there  is  a  considerable 
percentage  of  the  fat  absorbed  that  cannot  be  recovered  from  the  lymph 
of  the  thoracic  duct.  While  this  result  does  not  invalidate  the  conclusion 
stated  above  that  the  fat  passes  chiefly,  perhaps  entirely,  into  the  Iacteals, 
it  does  indicate  that  there  arc  some  factors  concerned  in  the  process  of  fat- 
absorption  that  are  at  present  unknown  to  us.  The  passage  of  the  fat- 
droplets  to  the  central  lacteal  is  not  difficult  to  understand.  The  adenoid 
tissue  of  the  stroma  is  penetrated  by  minute  unformed  lymph-channels  that 
are  doubtless  connected  with  the  central  lacteal.  In  each  villus  lymph  is 
continually  formed  from  the  circulating  blood,  so  that  there  must  be  a  slow 
stream  of  lymph  through  the  stroma  to  the  lacteal.  When  the  fat-droplets 
have  passed  through  the  epithelial  cells  (and  basement  membrane)  they  drop 
into  the  interstices  of  the  adenoid  tissue  and  are  carried  in  this  stream  into 
the  lacteal.  The  Iacteals  were  formerly  designated  as  the  "absorbents,"  under 
the  false  impression  that  they  attended  to  all  the  absorption  going  on  in  the 
intestines,  including  that  of  peptones,  sugars,  and  fats.  It  is  now  known  that 
their  action  under  ordinary  conditions  is  limited  to  the  absorption  of  fats. 

Absorption  of  "Water  and  Salts. — From  what  has  been  said  (p.  312)  it  is 
evident  that  absorption  of  water  takes  place  very  slightly,  if  at  all,  in  the 
-o.inael).      Whenever  soluble  substances,  such  as  peptones,  sugars,  or  salts,  are 


CHEMISTRY  OF  DIGESTION   AND   NUTRITION.  319 

absorbed  in  this  organ,  a  certain  amount  of  water  must  go  with  them,  but  the 
bulk  of  the  water  passes  out  of  the  pylorus.  In  the  small  intestine  absorp- 
tion of  water  and  of  inorganic  salts  evidently  takes  place  readily,and  accord- 
ing to  the  experiments  of  Kohmann  and  lleideuhaiu,  already  referred  to,  the 
laws  governing  their  absorption  are  different  from  what  we  should  expect  at 
first  sight  if  the  process  were  simply  one  of  diffusion.  The  differences  as 
regards  the  absorption  of  salts  are  especially  emphasized  by  the  experiments 
of  Heidenhain.1  Making  use  of  an  interesting  method,  for  which  reference 
must  be  made  to  the  original  paper,  Heidenhain  has  shown  that  not  only 
dilute  solutions,  but  solutions  of  nearly  the  same  osmotic  pressure  as  the 
blood  were  readily  absorbed.  Indeed,  specimens  of  the  animal's  own  serum 
introduced  into  a  loop  of  the  intestine  were  completely  absorbed,  although  in 
this  case  there  was  practically  no  difference  in  composition  between  the  liquid 
in  the  intestine  and  the  blood  of  the  animal.  In  another  paper  by  Heiden- 
hain2 he  has  proved  that  the  absorption  of  water  in  the  small  intestine,  when 
ordinary  amounts  are  ingested,  takes  place  entirely  through  the  blood-vessels 
of  the  villus,  and  not  through  the  lacteals;  when  larger  quantities  of  water 
are  swallowed,  a  small  part  may  be  absorbed  through  the  lacteals,  as  shown 
by  the  increased  lymph-flow,  but  by  far  the  larger  quantity  is  taken  up 
directly  by  the  blood. 

In  the  large  intestine  the  contents  become  progressively  more  solid  as  thev 
approach  the  rectum  ;  the  absorption  of  wrater  is  such  that  the  stream  is 
mainly  from  the  intestinal  contents  to  the  blood,  giving  us  a  phenomenon 
somewhat  similar  to  the  absorption  of  water  by  the  roots  of  a  plant.  This 
process  is  difficult  to  understand  upon  the  supposition  that  it  is  caused  by 
osmosis,  using  that  term  in  its  ordinary  sense,  unless  we  assume  that  it  is 
due  entirely  to  the  osmotic  pressure  of  the  indiffusible  proteids  of"  the  blood 
as  explained  on  p.  69. 

Composition  of  the  Feces. — The  feces  differ  widely  in  amount  and  in 
composition  with  the  character  of  the  food.  Upon  a  diet  comp< ^>v<\  exclu- 
sively of  meats  they  are  small  in  amount  and  dark  in  color;  with  an  ordinary 
mixed  diet  the  amount  is  increased,  and  it  is  largest  with  an  exclusively  vege- 
table diet,  especially  with  vegetables  containing  a  large  amount  of  indigest- 
ible material.  The  average  weight  of  the  feces  in  twenty-four  hours  upon  a 
mixed  diet  is  given  as  170  grains,  while  with  a  Vegetable  diet  it  may  amount 
to  as  much  as  400  or  500  grams.  The  quantitative  composition,  therefore,  will 
vary  greatly  with  the  diet.  Qualitatively,  we  find  in  the  \'wv^  the  following 
things:  (1)  Indigestible  material,  such  as  ligaments  of  meat  or  cellulose  from 
vegetables.  (2)  Undigested  material,  such  as  fragments  of  meat,  starch,  or  fats 
which  have  in  some  way  escaped  digestion.  Naturally,  the  quantity  of  this 
material  present  is  slight  under  normal  conditions.  Some  fats,  however,  are 
almost  always  found  in  feces,  either  as  neutral  fats  or  as  fatty  acids,  and  to 
a  small  extent  as  calcium  or  magnesium  soaps.     The  quantity  of  fat    found  is 

1  Pfliiger'a  Archiv fur  die  gesammle  Physiologic,  18{»4,  Bd.  '>*'<,  S.  579. 

2  Ibid.,  1888,  Bd.  43,  supplement. 


320  AN  AMERICAN    TEXT- HOOK    OE   PHYSIOLOGY. 

increased  by  an  increase  of  the  fats  in  the  fond.  (3)  Products  of  the  intes- 
tinal secretions.  Evidence  lias  accumulated  in  recent  years1  to  show  that 
the  l'rcv>  in  man  on  an  average  diet  arc  composed  mainly  of  the  material  of 
the  intestinal  secretions.  The  nitrogen  of  the  feces,  formerly  supposed  to 
represent  undigested  food,  seems  rather  to  have  its  origin  in  these  secretions, 
and,  therefore,  like  tin-  nitrogen  of  the  urine  represents  so  much  metabolism 
in  the  body.  (4)  Products  of  bacterial  decomposition.  The  most  character- 
istic of  these  products  arc  indol  and  skatol.  These  two  substances  are 
formed  normally  in  the  large  intestine  from  the  putrefaction  of  proteid 
material.  They  occur  always  together.  Indol  has  the  formula  CJLX, 
and  skatol,  which  is  a  methyl  indol.  the  formula  Cdf.X.  They  are  crystal- 
line bodies  possessing  a  disagreeable  fecal  odor;  this  is  epecially  true  of 
skatol,  to  which  the  odor  of  the  i'vfc<  is  mainly  due.  Indol  and  skatol 
are  eliminated  from  the  body  only  in  part  in  the  feces;  a  certain  propor- 
tion of  each  is  absorbed  into  the  blood  and  is  eliminated  in  a  modified  form 
through  the  urine — indol  as  indican  (indoxyl-sulphuricacid),  from  which  indigo 
was  formerly  made,  and  skatol  as  skatoxyl-sulphuric  acid  (see  Chemical  section 
for  further  information  as  to  the  chemistry  of  these  bodies).  (5)  Cholesteriu, 
which  is  found  always  in  small  amounts  and  is  probably  derived  from  the  bile. 
(0)  Excretin,  a  crystallizable,  non-nitrogenous  substance  to  which  the  formula 
C78H156S02  has  been  assigned,  is  found  in  minute  quantities.  (7)  Mucus  and 
epithelial  cells  thrown  off  from  the  intestinal  wall.  (8)  Pigment.  In  addition 
to  the  color  due  to  the  undigested  food  or  to  the  metallic  compounds  contained 
in  it,  there  is  normally  present  in  the  feces  a  pigment,  hydrobilirubin,  derived 
from  the  pigments  (bilirubin)  of  the  bile.  Hydrobilirubin  is  formed  from 
the  bilirubin  by  reduction  in  the  large  intestine.  (9)  Inorganic  salts — salts 
of  sodium,  potassium,  calcium,  magnesium,  and  iron.  The  importance  of 
the  calcium  anil  iron  salts  will  be  referred  to  in  a  subsequent  chapter, 
when  speaking  of  their  nutritive  importance.  (10)  Micro-organisms.  Great 
quantities  of  bacteria  of  different  kinds  are  found  in  the  W'cv^. 

In  addition  to  the  feces,  there  is  found  often  in  the  large  intestine  a 
quantity  of  gas  that  may  also  be  eliminated  through  the  rectum.  This  gas 
varies  in  composition.  The  following  constituents  have  been  determined  to 
occur  at  one  time  or  another:  CH4,  CO,,  H,  X,  H2S.  They  arise  mainly 
from  the  bacterial  fermentation  of  the  proteids,  although  some  of  the  N  may 
be  derived  from  air  swallowed  with  the  food. 

F.  Physiology  of  the  Liver  and  the  Spleen. 

The  liver  plays  an  important  part  in  the  general  nutrition  of  the  body;  its 
functions  are  manifold,  but  in  the  long  run  they  depend  upon  the  properties 
of  the  liver-cell,  which  constitutes  the  anatomical  and  physiological  unit  of  the 
organ.  These  cells  arc  seemingly  uniform  in  structure  throughout  the  whole 
Bubstance  of  the  liver,  but  to  understand  clearly  the  different  functions  they 
fulfil  one  must  have  a  clear  idea  of  their  anatomical  relations  to  one  another 

1  See  Prausnitz:  Zeit&chrift  fur  Biologie,  1897,  Bd.  35,  S.  335;  and  Tsuboi :  Ibid.,  S.  08. 


CHEMISTRY  OF  DIGESTION   AND   NUTRITION.  321 

and  to  the  blood-vessels,  the  lymphatics,  and  the  bile-ducts.  The  histology  of 
the  liver  Lobule,  and  the  relationship  of  the  portal  vein,  the  hepatic  artery,  and 
the  bile-duct  to  the  lobule,  must  be  obtained  from  the  text-books  upon  histol- 
ogy and  anatomy.  It  is  sufficient  here  to  recall  the  fact  that  each  lobule  is 
supplied  with  blood  coming  in  part  from  the  portal  vein  and  in  part  from  the 
hepatic  artery.  The  blood  from  the  former  source  contains  the  soluble  prod- 
ucts absorbed  from  the  alimentary  canal,  such  as  sugar  and  proteid,  and  these 
absorbed  products  are  submitted  to  the  metabolic  activity  of  the  liver-cells 
before  reaching  the  general  circulation.  The  hepatic  artery  brings  to  the  liver- 
cells  the  arterialized  blood  sent  out  into  the  systemic  circulation  from  the  left 
ventricle.  In  addition,  each  lobule  gives  origin  to  the  bile-capillaries  which 
arise  between  the  separate  cells  and  which  carry  off*  the  bile  formed  within 
the  cells.  In  accordance  with  these  facts,  the  physiology  of  the  liver-cell  falls 
naturally  into  two  parts — one  treating  of  the  formation,  composition,  and  physi- 
ological significance  of  bile,  and  the  other  dealing  with  the  metabolic  changes 
produced  in  the  mixed  blood  of  the  portal  vein  and  the  hepatic  artery  as  it  flows 
through  the  lobules.  In  this  latter  division  the  main  phenomena  to  be  studied 
are  the  formation  of  urea  and  the  formation  and  significance  of  glycogen. 

Bile. — From  a  physiological  standpoint,  bile  is  partly  an  excretion  carrying 
off"  certain  waste  products,  and  partly  a  digestive  secretion  playing  an  import- 
ant role  in  the  absorption  of  fats,  and  possibly  in  other  ways.  Bile  is  a  con- 
tinuous secretion,  but  in  animals  possessing  a  gall-bladder  its  ejection  into  the 
duodenum  is  intermittent.  For  the  details  of  the  mechanism  of  its  secretion, 
its  dependence  on  nerve-  and  blood-supply,  etc.,  the  reader  is  referred  to  the 
section  on  Secretion.  Bile  is  easily  obtained  from  living  animals  by  establishing 
a  fistula  of  the  bile-duct  or,  as  seems  preferable,  of  the  gall-bladder.  The 
latter  operation  has  been  performed  a  number  of  times  on  human  beings.  In 
some  cases  the  entire  supply  of  bile  has  been  diverted  in  this  way  to  the  ex- 
terior, and  it  is  an  interesting  physiological  fact  that  such  patients  may  con- 
tinue to  enjoy  fair  health,  showing  that,  whatever  part  the  bile  takes  normally 
in  digestion  and  absorption,  its  passage  into  the  intestine  is  not  absolutely 
necessary  to  the  nutrition  of  the  body.  The  quantity  of  bile  secreted  during 
the  day  has  been  estimated  for  human  beings  of  average  weight  (43  to  73  kilo- 
grams) as  varying  between  ;j<>»>  and  800  cubic  centimeters.  This  estimate  is 
based  upon  observations  on  cases  of  biliary  fistula.1  Chemical  analyses  of  the 
bile  show  that,  in  addition  to  the  water  and  salts,  it  contains  bile-pigments, 
bile-acids,  cholesterin,  lecithin,  neutral  fats  and  soaps,  sometimes  a  trace  of  urea, 
and  a  mucilaginous  nueleo-albumin  formerly  designated  improperly  as  mucin. 
The  last-mentioned  substance  is  not  formed  in  the  liver-cells,  but  is  added 
to  the  bile  by  the  mucous  membrane  of  the  bile-ducts  and  gall-bladder.  The 
quantity  of  these  substances  present  in  the  bile  must  vary  greatly  in  different 
animals  and   under  different  conditions.      As  an   illustration  of  their   relative 

1  Copeman  and  Winston:  Journal  of  Physiology,  1889,  vol.  x.  p.  213;   Robson :   Proceedings 
of  the  Royal  Society,  Loudon,  L890,  vol.  17,  p.  499;    Pfaff  and  Balch     Journalof  Experimental 
Medicine,  L897,  vol.  ii.  p.  49. 
Vol.  t.     21 


322  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

importance  in  human  bile  and  of  the  limits  of  variation  the  two  following 
analyses  by  Hammarsten  J  may  be  quoted : 

i.  11. 

Solids      2.520  2.840 

Water 97.480  97.160 

Mucin  and  pigment      0.529  0.910 

Bile-salts 0.931  0.814 

Taurocholate 0.3034  0.053 

Glycocholate 0.6276  0.761 

Fatty  acids  from  soap 0.1230  0.024 

Cbolesterin 0.0630  0.096 

Lecithin 
Fat 

Soluble  salts 0.8070  0.8051 

Insoluble  salts        0.0250  0.0411 


}      0.0220  0.1286 


The  color  of  bile  varies  in  different  animals  according  to  the  preponderance 
of  one  or  the  other  of  the  main  bile-pigments,  bilirubin  and  bUiverdin.  The 
6ile  of  carnivorous  animals  has  usually  a  bright  golden  color,  owing  to  the  pres- 
ence of  bilirubin,  while  that  of  the  herbivora  is  a  bright  green  from  the 
biliverdin.  The  color  of  human  bile  seems  to  vary  :  according  to  some  author- 
ities, it  is  yellow  or  brownish  yellow,  and  this  seems  especially  true  of  the  bile 
as  found  in  the  gall-bladder  of  the  cadaver  ;  according  to  others,  it  is  of  a  dark- 
olive  color  with  the  greenish  tint  predominating.  Its  reaction  is  feebly  alka- 
line, and  its  specific  gravity  varies  in  human  bile  from  1050  or  1040  to  1010. 
1 1  u  n  iau  bile  does  not  give  a  distinctive  absorption  spectrum,  but  the  bile  of  some 
herbivora,  after  exposure  to  the  air  at  least,  gives  a  characteristic  spectrum. 
The  individual  constituents  of  the  bile  will  now  be  described  more  in  detail, 
but  with  reference  mainly  to  their  origin,  fate,  and  function  in  the  body.  For 
a  description  of  their  strictly  chemical  properties  and  reactions  reference  must 
be  made  to  the  Chemical  section. 

Bile-pigments. — Bile,  according  to  the  animal  from  which  it  is  obtained, 
contains  one  or  the  other,  or  a  mixture,  of  the  two  pigments  bilirubin  and 
biliverdin.  Biliverdin  is  supposed  to  stand  to  bilirubin  in  the  relation  of  an 
oxidation  product.  Bilirubin  is  given  the  formula  Ci6H18N203,  and  biliverdin 
(',,  H^X/)4,  the  latter  being  prepared  readily  from  pure  specimens  of  the 
former  by  oxidation.  These  pigments  give  a  characteristic  reaction,  known 
as"Gmelin's  reaction,"  with  nitric  acid  containing  some  nitrous  acid  (nitric 
acid  with  a  yellow  color).  If  a  drop  of  bile  and  a  drop  of  nitric  acid  are 
brought  into  contact,  the  former  undergoes  a  succession  of  color  changes,  the 
order  being  green,  blue,  violet,  red,  and  reddish  yellow.  The  play  of  colors 
is  due  to  successive  oxidations  of  the  bile-pigments;  starting  with  bilirubin, 
the  first  stage  (green)  is  due  to  the  formation  of  biliverdin.  The  pigments 
firmed  in  some  of  the  other  stages  have  been  isolated  and  named.  The 
reaction  is  very  delicate,  and  it  is  often  used  to  detect  the  presence  of  bile- 
pigments  in  other  liquids — urine,  for  example.  The  bile-pigments  originate 
i Reported  in  Gentralblati  fur  Physiologic,  1894,  No.  v. 


CHEMISTRY  OF  DIGESTION  AND    NUTRITION.  323 

from  haemoglobin.  This  origin  was  first  indicated  by  the  fact  that  in  old 
blood-clots  or  in  extravasations  there  was  found  a  crystalline  product,  the 
so-called  "  haematoidin,"  which  was  undoubtedly  derived  from  haemoglobin, 
and  which  upon  more  careful  examination  was  proved  to  be  identical  with 
bilirubin.  This  origin,  which  has  since  been  made  probable  by  other  reac- 
tions, is  now  universally  accepted.  It  is  supposed  that  when  the  blood- 
corpuscles  go  to  pieces  in  the  circulation  (p.  45)  the  haemoglobin  is  brought  to 
the  liver,  and  then,  under  the  influence  of  the  liver-cells,  is  converted  t<>  an 
iron-free  compound,  bilirubin  or  biliverdin.  It  is  very  significant  to  find  that 
the  iron  separated  by  this  means  from  the  haemoglobin  is  for  the  most  part 
retained  in  the  liver,  a  small  portion  only  being  secreted  in  the  bile.  It  seems 
probable  that  the  iron  held  back  in  the  liver  is  again  used  in  some  way  to 
make  new  haemoglobin  in  the  haematopoietic  organs.  The  bile-pigments  are 
carried  in  the  bile  to  the  duodenum  and  are  mixed  with  the  food  in  its  long 
passage  through  the  intestine.  Under  normal  conditions  neither  bilirubin  nor 
biliverdin  is  found  in  the  feces,  but  in  their  place  is  found  a  reduction  pro- 
duct, hydrobilirubin,  formed  in  the  large  intestine.  Moreover,  it  is  believed 
that  some  of  the  bile-pigment  is  reabsorbed  as  it  passes  along  the  intestine, 
is  carried  to  the  liver  in  the  portal  blood,  and  is  again  eliminated.  That 
this  action  occurs,  or  may  occur,  has  been  made  probable  by  experiments  "I 
Wertheimer l  on  dogs.  It  happens  that  sheep's  bile  contains  a  pigment 
(cholohsematin)  that  gives  a  characteristic  spectrum.  II'  some  of  this  pig- 
ment is  injected  into  the  mesenteric  veins  of  a  dog,  it  is  eliminated  while 
passing  through  the  liver,  and  can  be  recognized  unchanged  in  the  bile. 
The  value  of  this  "circulation  of  the  bile,"  so  far  as  the  pigments  are  con- 
cerned, is  not  apparent. 

Bile-acids. — "Bile-acids"  is  the  name  given  to  two  organic  acids,  glyco- 
eholic and  taurocholic,  which  are  always  present  in  bile,  and,  indeed,  form 
very  important  constituents  of  that  secretion  ;  they  occur  in  the  form  of  their 
respective  sodium  salts.  In  human  bile  both  acids  are  usually  found,  but 
the  proportion  of  taurocholate  is  variable,  and  in  some  cases  this  latter  acid 
may  be  absent  altogether.  Among  herbivora  the  glyeocholate  predominates 
as  a  ride,  although  there  are  some  exceptions  ;  among  the  carnivora,  on  the 
other  hand,  taurocholate  occurs  usually  in  greater  quantities,  and  i'i  the  dog's 
bile  it  is  present  alone.  Glycoeholic  acid  has  the  formula  ( '  J  .  |;!N(  >,.,,  and 
taurocholic  acid  has  the  formula  CoJI^NSOj.  Each  of  them  can  be  obtained 
in  the  form  of  crystals.'  When  boiled  with  acids  or  alkalies  these  acids  take 
up  water  and  undergo  hydrolytic  cleavage,  the  reaction  being  represented  by 
the  following  equations: 

c2Sh43no6    +  h2o  =  C24H40O,  +  ch2(NH2)COOH. 

Glycoeholic  acid.  Cfaolic  acid.         Glycocoll  (amido-acetic  add). 


C26H45NS07  +    H20  034H4()O,    +   fVH.XIl ,S( )...( )U 

feurocholic  acid.  Cholicacid.  Taurin  (amido-ethyl 

Bulphonic  acid 

1  Archives  de  Physiologie  normale  ei  paihologique,  1892,  p.  577. 


•°,24  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

Tlnse  reactions  are  interesting  not  only  in  that  they  throw  light  on  the  structure 
of  the  acids,  but  also  because  similar  reactions  doubtless  take  place  in  the  intes- 
tine, cholic  acid  having  been  detected  in  the  intestinal  contents.  As  the  for- 
mulas show,  cholic  acid  is  formed  in  the  decomposition  of  each  acid,  and  we 
may  regard  the  bile-acids  as  compounds  produced  by  the  synthetic  union  of 
cholic  acid  with  glycocoll  in  the  one  case  and  with  taurin  in  the  other. 
Cholic  acid  or  its  compounds,  the  bile-acids,  are  usually  detected  in  suspected 
liquids  by  the  well-known  Pettenkofer  reaction.  As  usually  performed,  the 
test  is  made  by  adding  to  the  liquid  a  few  drops  of  a  10  per  cent,  solution  of 
cane-sugar  and  then  strong  sulphuric  acid.  The  latter  must  be  added  carefully 
and  the  temperature  be  kept  below  70°  C.  If  bile-acids  arc  present,  the  liquid 
assumes  a  beautiful  red-violet  color.  It  is  now  known  that  the  reaction  con- 
sists in  the  formation  of  a  substance  (furfurol)  by  the  action  of  the  acid  on 
sugar,  which  then  reacts  with  the  bile-acids.  The  bile-acids  are  formed 
directly  in  the  liver-cells.  This  fact,  which  was  for  a  long  time  the  subject  of 
discussion,  has  been  demonstrated  in  recent  years  by  an  important  series  of 
researches  made  upon  birds.  It  has  been  shown  that  if  the  bile-duct  is  ligated 
in  these  animals,  the  bile  formed  is  reabsorbed  and  bile-acids  and  pigments 
may  be  detected  in  the  urine  and  the  blood.  If,  however,  the  liver  is  com- 
pletely extirpated,  then  no  trace  of  either  bile-acids  or  bile-pigments  can  be 
found  in  the  blood  or  the  urine,  showing  that  these  substances  are  not 
formed  elsewhere  in  the  body  than  in  the  liver.  It  is  more  difficult  to  ascer- 
tain from  what  substances  they  arc  formed.  The  fact  that  glycocoll  and 
taurin  contain  nitrogen,  and  that  the  latter  contains  sulphur,  indicates  that 
some  proteid  or  albuminoid  constituent  is  broken  down  during  their  pro- 
duction. 

A  circumstance  of  considerable  physiological  significance  is  that  these  acids 
or  their  decomposition  products  are  absorbed  in  part  from  the  intestine  and 
are  again  secreted  by  the  liver:  as  in  the  case  of  the  pigments,  there  is  an 
intestinal-hepatic  circulation.  The  value  of  this  reabsorption  may  lie  in  the 
fact  that  the  bile-acids  constitute  a  very  efficient  stimulus  to  the  bile-secreting 
activity  of  the  cells,  being  one  of  the  best  of  cholagogues,  or  it  may  be  that  it 
economizes  material.  From  what  we  know  of  the  history  of  the  bile-acids 
it  is  evident  that  they  are  not  to  be  considered  as  excreta:  they  have  some 
important  function  to  fulfil.  The  following  suggestions  as  to  their  value  have 
been  made:  In  the  first  place,  they  serve  as  a  menstruum  for  dissolving  the 
cholesterin  which  is  constantly  preseut  in  the  bile  and  which  is  an  excretion 
to  be  removed  ;  secondly,  they  facilitate  the  absorption  of  fats  from  the  intes- 
tine. The  value  of  bile  in  fat -absorption  will  presently  be  referred  to  more 
in  detail.  It  is  an  undoubted  fact  that  when  bile  is  shut  off  from  the  intes- 
tine the  absorption  of  fats  is  very  much  diminished,  and  it  has  been  shown 
that  this  action  of  the  bile  in  fat  absorption  is  owing  to  the  presence  of  the 
bile-acids. 

Cholesterin. — Cholesterin  is  a  non-nitrogenous  substance  of  the  formula 
C26H44G  or  CyE^OH).     It  is  a  constant  constituent  of  the  bile,  although  it 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  325 

occurs  in  variable  quantities.  Cholesterin  is  very  widely  distributed  in  the 
body,  being  found  especially  in  the  white  matter  (medullary  substance)  of 
nerve-fibres.  It  seems,  moreover,  to  be  a  constant  constituent  of  all  animal 
and  plant  cells.  It  is  assumed  that  cholesterin  is  not  formed  in  the  liver, 
but  that  it  is  eliminated  by  the  liver-cells  from  the  blood,  which  collects  it 
from  the  various  tissues  of  the  body.  That  it  is  an  excretion  is  indicated  by 
the  fact  that  it  is  eliminated  unchanged  in  the  feces.  Cholesterin  is  insoluble 
in  water  or  in  dilute  saline  liquids,  and  is  held  in  solution  in  the  bile  by 
means  of  the  bile-acids.  We  must  regard  it  as  a  waste  product  of  cell-life, 
formed  probably  in  minute  quantities,  and  excreted  mainly  through  the 
liver.  It  is  partly  eliminated  through  the  skin,  in  the  sebaceous  and  sweat 
secretions,  and  in  the  milk. 

Lecithin,  Fats,  and.  Nucleo-albumin. — Lecithin  also  seems  to  be  present, 
generally  in  small  quantities,  in  the  cells  of  the  various  tissues,  but  it  occurs 
especially  in  the  white  matter  of  nerve-fibres.  It  is  probable,  therefore,  that, 
so  far  as  it  is  found  in  the  bile,  it  represents  a  waste  product  formed  in 
different  parts  of  the  body  and  eliminated  through  the  bile.  The  special 
importance,  if  any,  of  the  small  proportion  of  fats  and  fatty  acids  in  the  bile 
is  unknown.  The  ropy,  mucilaginous  character  of  bile  is  due  to  the  presence 
of  a  body  formed  in  the  bile-ducts  and  gall-bladder.  This  substance  was 
formerly  designated  as  mucin,  but  it  is  now  known  that  in  ox-bile  at  least 
it  is  not  a  true  mucin,  but  is  a  nucleo-albumin  (see  Chemical  section).  Ham- 
marsten  reports  that  in  human  bile  some  true  mucin  is  found.  Outside  the 
fact  that  it  makes  the  bile  viscous,  this  constituent  is  not  known  to  possess 
any  especial  physiological  significance. 

General  Physiological  Importance  of  Bile. — The  physiological  value 
of  bile  has  been  referred  to  in  speaking  of  its  several  constituents,  but  it  will 
be  convenient  here  to  restate  these  facts  and  to  add  a  few  remarks  of  general 
interest.  Bile  is  of  importance  as  an  excretion  in  that  it  removes  from  the 
body  waste  products  of  metabolism,  such  as  cholesterin,  lecithin,  and  bile- 
pigments.  With  reference  to  the  pigments,  there  is  evidence  to  show  that  a 
part  at  least  may  be  reabsorbed  while  passing  through  the  intestine,  and  be 
used  again  in  some  way  in  the  body.  The  bile-acids  represent  end-products 
of  metabolism  involving  the  proteids  of  the  liver-cells,  but  they  are  undoubt- 
edly reabsorbed  in  part,  and  cannot  be  regarded  merely  as  excreta.  As  a 
digestive  secretion  the  most  important  function  attributed  to  the  bile  is  the 
part  it  takes  in  the  digestion  of  fits.  Tn  the  first  place,  it  aids  in  the  splitting 
of  a  part  of  the  neutral  fats  and  the  subsequent  emulsification  of  the  re- 
mainder (p.  307).  More  than  this,  bile  aids  materially  in  the  absorption  of  the 
digested  fats.  A  number  of  observers  have  shown  that  when  a  permanent 
biliary  fistula  is  made,  and  the  bile  is  thus  prevented  from  reaching  the  intes- 
tinal canal,  a  large  proportion  of  the  flit  of  the  food  escapes  absorption  and 
is  found  in  the  \\'t-vs.  This  property  of  the  bile  IS  known  to  depend  upon 
the  bile-acids  it  contains,  but  how  they  act  is  not  clearly  understood.  It  was 
formerly  believed,  on  the  basis  of  some  experiments  by   von    Westinghausen, 


326  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

that  the  bile-acids  dissolve  or  mix  with  the  fats  and  at  the  same  time  moisten 
the  mucous  membrane,  and  for  these  reasons  aid  in  bringing  the  fat  into 
immediate  contact  with  the  epithelial  cells.  It  was  stated,  for  instance, 
that  oil  rises  higher  in  capillary  tubes  moistened  with  bile  than  in  similar 
tubes  moistened  with  water,  and  that  oil  will  filter  more  readily  through 
paper  moistened  with  bile  than  through  paper  wet  with  water.  Groper,1  who 
repeated  these  experiments,  finds  that  they  are  erroneous.  It  seems 
certain,  however,  that  the  bile-aeids  enable  the  bile  to  hold  in  solution 
a  considerable  quantity  of  fatty  acids,  and  possibly  this  fact  explains  its 
connection  with  fat  absorption.  It  was  formerly  believed  that  bile  is 
also  of  great  importance  in  restraining-  the  processes  of  putrefaction  in 
the  intestine.  It  was  asserted  that  bile  is  an  efficient  antiseptic,  and 
that  this  property  comes  into  use  normally  in  preventing  excessive  putre- 
faction. Bacteriological  experiments  made  by  a  number  of  observers  have 
shown,  however,  that  bile  itself  has  very  feeble  antiseptic  properties,  as  is 
indicated  by  the  fact  that  it  putrefies  readily.  The  free  bile-aeids  and  cholalic 
acid  do  have  a  direct  retarding  effect  upon  putrefactions  outside  the  body  ; 
but  this  action  is  not  very  pronounced,  and  has  not  been  demonstrated  satis- 
factorily for  bile  itself.  It  seems  to  be  generally  true  that  in  cases  of  biliary 
fistula  the  feces  have  a  very  fetid  odor  when  meat  and  fat  are  taken  in  the 
food.  But  the  increased  putrefaction  in  these  cases  may  possibly  be  due  to 
some  indirect  result  of  the  withdrawal  of  bile.  It  has  been  suggested,  for 
instance,  that  the  deficient  absorption  of  fat  that  follows  upon  the  removal 
of  the  bile  results  in  the  proteid  and  carbohydrate  material  becoming  coated 
with  an  insoluble  layer  of  fat,  so  that  the  penetration  of  the  digestive  enzymes 
is  retarded  and  greater  opportunity  is  given  for  the  action  of  bacteria.  We 
may  conclude,  therefore,  that  while  there  does  not  seem  to  be  sufficient  warrant 
at  present  for  believing  that  the  bile  exerts  a  direct  antiseptic  action  upon  the 
intestinal  contents,  nevertheless  its  presence  limits  in  some  way  the  extent  of 
putrefaction.  Lastly,  bile  takes  a  direct  part  in  suspending  or  destroying 
peptic  digestion  in  the  acid  chyme  forced  from  the  stomach  into  the  duodenum. 
The  chyme  meeting  with  bile  and  pancreatic  juice  is  neutralized  or  is  made 
alkaline,  which  alone  would  prevent  further  peptonization.  Moreover,  when 
chyme  and  bile  are  mixed  a  precipitate  occurs,  consisting  partly  of  proteids 
(proteoses  and  syntonin)  and  partly  of  bile-acids.  It  is  probable  that  pepsin, 
according  to  its  well-known  property,  is  thrown  down  in  this  flocculent  pre- 
cipitate and,  as  it  were,  prepared   for  its  destruction. 

Glycogen. — One  of  the  most  important  functions  of  the  liver  is  the  for- 
mation of  glycogen.  This  substance  was  found  in  the  liver  in  1857  by  Claude 
Bernard,  and  is  one  of  several  brilliant  discoveries  made  by  him.  Glycogen  has 
the  formula  (C6H10O5)n,  which  is  also  the  general  formula  given  to  vegetable 
starch;  glycogen  is  therefore  frequently  spoken  of  as  "animal  starch."  It 
gives,  however,  a  port-wine-red  color  with  iodine  solutions,  instead  of  the 
familiar  deep  blue  of  vegetable  starch,  and  this  reaction  serves  to  detect  glyco- 
1  Arrhiv  fur  Anatomie  wnd  Physiologic  ("Physiol.  Abtlieilung"),  1889,  S.  505. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  327 

gen  not  only  in  its  solutions,  but  also  in  the  liver-cells.  Glycogen  is  readily 
soluble  in  water,  and  the  solutions  have  a  characteristic  opalescent  appearance. 
Like  starch,  glycogen  is  acted  upon  by  ptyalin  and  araylopsin,  and  the  end- 
products  are  apparently  the  sam< — namely,  maltose,  or  maltose  and  some 
dextrin.  For  a  more  complete  account  of  the  chemical  relations  of  glycogen 
reference  must  be  made  to  the  Chemical  section. 

Occurrence  of  Glycogen  in  the  Liver. — Glycogen  can  be  detected  in 
the  liver-cells  microscopically.  It'  the  liver  of  a  dog  is  removed  twelve  or 
fourteen  hours  after  a  hearty  meal,  hardened  in  alcohol,  and  sectioned,  the 
liver-cells  will  be  found  to  contain  clumps  of  clear  material  which  give  the 
iodine  reaction  for  glycogen.  Even  when  distinct  aggregations  of  the  glycogen 
cannot  be  made  out,  its  presence  in  the  cells  is  shown  by  the  red  reaction  with 
iodine.  By  this  simple  method  one  can  demonstrate  the  important  fact  that 
the  amount  of  glycogen  in  the  liver  increases  after  meals  and  decreases  again 
during  the  fasting  hours,  and  if  the  fast  is  sufficieutly  prolonged  it  may  dis- 
appear altogether.  This  fact  is,  however,  shown  more  satisfactorily  by  quanti- 
tative determinations,  by  chemical  means,  of  the  total  glycogen  present.  The 
amount  of  glycogen  present  in  the  liver  is  quite  variable,  being  influenced  by 
such  conditions  as  the  character  and  amount  of  the  food,  muscular  exercise, 
bodv-temperature,  drugs,  etc.  From  determinations  made  upon  various 
animals  it  may  be  said  that  the  average  amount  lies  between  1.5  and  4  per 
cent,  of  the  weight  of  the  liver.  But  this  amount  may  be  increased  great  ly 
bv  feeding  upon  a  diet  largely  made  up  of  carbohydrates.  It  is  said  that  in 
the  dog  the  total  amount  of  liver-glycogen  may  be  raised  to  17  per  cent.,  and 
in  the  rabbit  to  27  per  cent.,  by  this  means,  while  it  is  estimated  for  man 
(Xeumeister)  that  the  quantity  may  be  increased  to  at  least  10  per  cent.  It 
is  usually  believed  that  glycogen  exists  as  such  in  the  liver-cells,  being  depos- 
ited in  the  substance  of  the  cytoplasm.  Reasons  have  been  brought  forward 
recently  to  show  that  possibly  this  is  not  strictly  true,  but  that  the  glycogen  is 
held  in  some  sort  of  weak  chemical  combination.  It  has  been  shown,  for 
instance,  that  although  glycogen  is  easily  soluble  in  cold  water,  it  cannot  be 
extracted  readily  from  the  liver-cells  by  this  agent.  One  musl  use  hoi  water, 
salts  of  the  heavy  metals,  and  other  similar  means  that  may  be  supposed  to 
break  up  the  combination  in  which  the  glycogen  exists.  For  practical  purposes, 
however,  we  may  speak  of  the  glycogen  as  lying  free  in  the  liver-cells,  jusl  as 
we  speak  of  haemoglobin  existing  as  such  in  the  red  corpuscles,  although  it  is 
probably  held  in  some  sort  of  combination. 

Origin  of  Glycogen. — To  understand  clearly  the  views  held  as  to  the 
origin  of  liver  glycogen,  it  will  be  necessary  to  describe  briefly  the  effect  of 
the  different  food-stulf-   upon    its   formation. 

Effect  of  Carbohydrates  <>n  the  Amount  of  Glycogen. — The  amount  of 
glycogen  in  the  liver  is  affected  very  quickly  by  the  quantity  of  carbohydrates 
in  the  food.  It'  the  carbohydrates  are  given  in  exec--,  the  supply  of  glycogen 
maybe  increased  largely  beyond  the  average  amount  present,  as  ha-  been  stated 
above.      Investigation  of  the  different  sugars  has  shown  that  dextrose,  levulose, 


328  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

saccharose  (cane-sugar),  and  maltose  arc  unquestionably  direct  glycogen-formers, 
that  i-.  that  glycogen  is  formed  directly  from  them  or  from  the  products  into 
which  they  are  converted  during  digestion.  Now,  our  studies  in  digestion  have 
shown  that  the  starches  are  converted  into  maltose,  or  maltose  and  dextrin, 
during  digestion,  and,  further,  that  these  substances  are  changed  or  inverted  to 
the  simpler  sugar  dextrose  during  absorption.  ( lane-sugar,  which  forms  such 
an  important  part  of  our  diet,  is  inverted  in  the  intestine  into  dextrose  and 
levulose,  ami  is  absorbed  in  these  forms.  It  is  evident,  therefore,  that  the 
hulk  of  our  carbohydrate  food  reaches  the  liver  as  dextrose,  or  as  dextrose 
and  levulose,  and  these  forms  of  sugar  must  he  converted  into  glycogen  in  the 
liver-cells  by  a  process  of  dehydration  such  as  may  he  represented  in  substance 
by  the  formula  <  ',1 1 ,.,<),-  II, ()  =  C6H1()Ov  There  is  no  doubt  that  both 
dextrose  and  levulose  increase  markedly  the  amount  of  glycogen  in  the  liver  ; 
and,  since  cane-sugar  is  inverted  in  the  intestine  before  absorption,  it  also  must 
he  a  good  glycogen-former — a  fact  that  has  been  abundantly  demonstrated 
by  direct  experiment.  Lusk  '  has  shown,  however,  that  if  cane-sugar  is  in- 
jected under  the  skin,  it  has  a  very  feeble  effect  in  the  way  of  increasing  the 
amount  of  glycogen  in  the  liver,  since  under  these  conditions  it  is  probably 
absorbed  into  the  blood  without  undergoing  inversion.  Experiments  with  sub- 
cutaneous injection  of  lactose  gave  similar  results,  and  it  is  generally  believed 
that  the  liver-cells  cannot  convert  the  double  sugars  to  glycogen,  at  least  not 
readily;  hence  the  value  of  the  hydrolysis  of  these  sugars  in  the  alimentary 
canal  before  absorption.  The  relations  of  lactose  to  glycogen-formation  have 
not  been  determined  satisfactorily.  If  it  contributes  at  all  to  the  direct  forma- 
tion of  glycogen,  it  is  certainly  less  efficient  than  dextrose,  levulose,  or  cane- 
sugar.  When  the  proportion  of  lactose  in  the  diet  is  much  increased,  it  quickly 
begins  to  appear  in  the  urine,  showing  that  the  limit  of  its  consumption  in  the 
body  is  soon  reached.  This  latter  fact  is  somewhat  singular,  since  in  infancy 
especially  milk-sugar  forms  a  constant  and  important  item  of  our  diet,  and 
one  would  suppose  that  it  is  especially  adapted  to  the  needs  of  the  body. 

Effect  of  Proteids  <>n  Glyeogen-formaiion. — It  was  pointed  out  by  Bernard, 
in  his  first  studies  upon  glycogen-formation,  that  the  liver  can  produce  glycogen 
from  proteid  food.  This  conclusion  has  since  been  verified  by  more  exact 
investigations.  When  an  animal  is  fed  upon  a  diet  of  proteid  alone,  or  on 
proteid  and  gelatin,  the  carbohydrates  being  entirely  excluded,  glycogen  is  still 
formed  in  the  liver,  although  in  smaller  amounts  than  in  the  case  of  carbohy- 
drate foods.  This  is  an  important  fact  to  remember  in  studying  the  metabo- 
lism of  the  proteids  in  the  body,  for,  as  glycogen  is  a  carbohydrate  and  con- 
tains no  nitrogen,  it  implies  that  the  proteid  molecule  is  dissociated  into  a 
nitrogenous  and  a  non-nitrogenous  part,  the  latter  being  converted  to  glycogen 
by  the  liver-cells.  The  possibility  of  the  production  of  glycogen  from  proteids 
accord-  with  a  well-known  fact  in  medical  practice  with  reference  to  the  path- 
ological condition  known  as  diabetes.  In  this  disease  sugar  is  excreted  in  the 
urine,  sometime-;  in  large  quantities.  As  the  sugar  of  the  blood  is  believed 
1  Voit:  Zeitachrift  fur  Biologie,  1891,  xxviii.  B.  285. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  329 

to  be  formed  ordinarily  from  the  carbohydrates  in  the  food,  it  was  thought 
that  by  excluding  this  food-stuff  from  the  diet  the  excretion  of  sugar  might 

be  prevented.  It  has  been  found,  however,  that  in  severe  eases  at  least 
sugar  continues  to  be  present  in  the  urine  even  upon  a  pure  proteid  diet.  If 
we  suppose  that  some  of  the  proteid  goes  to  form  glycogen,  the  result  ob- 
served is  explained,  for  the  glycogen,  as  will  be  explained  presently,  is  finally 
converted  to  sugar  and  is  given  oft'  to  the  blood.  An  interesting  additional 
fact  that  points  to  the  same  conclusion  is  that  the  percentage  of  sugar  in  the 
blood  remains  practically  constant  after  prolonged  starvation,  at  a  time  when 
the  animal  is  living  at  the  expense  of  the  proteids  and  fats  of  its  own  body. 

Effect  of  Fats  and  other  Substances  upon  Glyeogen-formatwn. —  It  has  been 
found  that  fats  take  no  part  in  the  formation  of  liver  glycogen.  Some 
attempts  have  been  made  to  prove  that  fat  in  the  body,  and  particularly  in 
the  liver,  may  be  converted  to  sugar,  but  the  evidence  at  present  seems  to  be 
against  this  possibility.1 

The  Function  of  Glycogen  :  Glycogenic  Theory. — The  meaning  of  the 
formation  of  glycogen  in  the  liver  has  been,  and  still  is,  the  subject  of  discus- 
sion. The  view  advanced  first  by  Bernard  is  perhaps  most  generally  accepted. 
According  to  Bernard,  glycogen  forms  a  temporary  reserve  supply  of  carbo- 
hydrate material  that  is  laid  up  in  the  liver  during  digestion  and  is  gradually 
made  use  of  in  the  intervals  between  meals.  During  digestion  the  carbohy- 
drate food  is  absorbed  into  the  blood  of  the  portal  system  as  dextrose  or  as 
dextrose  and  levulose.  If  these  passed  through  the  liver  unchanged,  the  con- 
tents of  the  systemic  blood  in  sugar  would  be  increased  perceptibly.  It  is  now 
known  that  when  the  percentage  of  sugar  in  the  blood  rises  above  a  certain 
low  limit,  the  excess  will  be  excreted  through  the  kidney  and  will  be  lost. 
But  as  the  blood  from  the  digestive  organs  passes  through  the  liver  the  ex- 
cess of  sugar  is  abstracted  from  the  blood  by  the  liver-cells,  is  dehydrated  to 
make  glycogen,  and  is  retained  in  the  cells  in  this  form  for  a  short  period. 
From  time  to  time  the  glycogen  is  reconverted  into  sugar  (dextrose)  and  is 
given  off  to  the  blood.  By  this  means  the  percentage  of  sugar  in  the  systemic 
blood  is  kept  nearly  constant  (0.1  to  0.2  per  cent.)  and  within  limits  best 
adapted  for  the  use  of  the  tissues.  The  great  importance  of  the  formation  of 
glycogen  and  the  consequent  conservation  of  the  sugar-supply  of  the  tissues  will 
be  more  evident  when  we  come  to  consider  the  nutritive  value  of  carbohydrate 
food.  Carbohydrates  form  the  bulk  of  our  usual  diet,  and  the  proper  regula- 
tion of  the  supply  to  the  tissues  is  therefore  of  vital  importance  in  the  main- 
tenance of  a  normal  healthy  condition.  The  second  part  of  this  theory,  which 
holds  that  the  glycogen  is  reconverted  to  dextrose,  is  supported  by  observations 

Upon  livers  removed  from  the  body.      It    has   been   found  that  shortly  after  the 

removal  of  the  liver  the  supply  of  glycogen  begins  t<>  disappear  and  a  corre- 
sponding increase  in  dextrose  occurs.  Within  a  comparatively  short  time  all 
the  glycogen  is  gone  and  only  dextrose  is  found.      It  is  for  this  reason  that  in 

1  Kumagawa  ami  Miura:   Arehiv  fur  Anatomie  und  Physiologie  ("Physiol.  Abtheilung"), 

1  s'. is,  s.  431,  contains  also  reference  to  the  literature  of  the  subject. 


330  AN    AMERICAN   TEXT-BOOK   OE   PHYSIOLOGY. 

the  estimation  of  glycogen  in  the  liver  it  is  necessary  to  mince  the  organ  and  to 
throw  it  into  boiling  water  as  quickly  as  possible,  since  by  this  means  the  liver- 
eel].-  are  killed  and  the  conversion  of  the  glycogen  is  stopped.  How  the 
glycogen  is  changed  to  dextrose  by  the  liver  is  a  matter  not  fully  explained. 
According  to  some  authors,  the  conversion  is  due  to  an  enzyme  produced  in 
the  liver.  Extracts  of  liver,  as  of  some  other  tissues,  do  yield  an  anxiolytic 
enzyme  that  changes  glycogen  to  dextrose.1  It  is  possible,  therefore,  that 
the  conversion  of  glycogen  to  dextrose  is  effected  by  a  special  enzyme 
produced  in  the  liver-cells.  In  this  description  of  the  origin  and  meaning 
of  the  liver  glycogen  reference  has  been  made  only  to  the  glycogen  derived 
directly  from  digested  carbohydrates.  The  glycogen  derived  from  proteid 
foods,  once  it  is  formed  in  the  liver,  has,  of  course,  the  same  functions  to  fulfil. 
It  is  converted  into  sugar,  and  eventually  is  oxidized  in  the  tissues.  For  the 
sake  of  completeness  it  may  be  well  to  add  that  some  of  the  sugar  of  the  blood 
firmed  from  the  glycogen  may  under  certain  conditions  be  converted  into  fat  in 
the  adipose  tissues,  instead  of  being  burnt,  and  in  this  way  it  may  be  retained 
in  the  body  as  a  reserve  supply  of  food  of  a  more  stable  character  than  is  the 
glycogen. 

Glycogen  in  the  Muscles  and  other  Tissues. — The  history  of  glycogen  is 
not  complete  without  some  reference  to  its  occurrence  in  the  muscles.  Glycogen 
is,  in  fact,  found  iu  various  places  in  the  body,  and  is  widely  distributed  through- 
out the  animal  kingdom.  It  occurs,  for  example,  in  leucocytes,  in  the  placenta, 
in  the  rapidly-growing  tissues  of  the  embryo,  and  in  considerable  abundance  in 
the  oyster  and  other  molluscs.  But  in  our  bodies  and  in  those  of  the  mam- 
mals generally  the  most  significant  occurrence  of  glycogen,  outside  the  liver, 
is  in  the  voluntary  muscles,  of  which  glycogen  forms  a  normal  constituent.  It 
has  been  estimated  that  the  percentage  of  glycogen  in  resting  muscle  varies 
from  0.5  to  0.9  per  cent.,  and  that  in  the  musculature  of  the  whole  body  there 
may  be  contained  an  amount  of  glycogen  equal  to  that  in  the  liver  itself. 
Apparently  muscular  tissue,  as  well  as  liver-tissue,  has  a  glycogenetie  func- 
tion— that  is,  it  is  capable  of  laving  up  a  supply  of  glycogen  from  the  sugar 
brought  to  it  by  the  blood.  The  glycogenetie  function  of  muscle  has  been 
demonstrated  directly  by  Kulz,-  who  has  shown  that  an  isolated  muscle  irrigated 
with  an  artificial  supply  of  blood  to  which  dextrose  had  been  added  is  capable 
of  changing  the  dextrose  to  glycogen,  as  shown  by  the  increase  in  the  latter  sub- 
stance in  the  muscle  after  irrigation.  Muscle  glycogen  is  to  be  looked  upon, 
probably,  for  reasons  to  be  mentioned  in  the  next  paragraph,  as  a  temporary 
and  local  reserve  supply  of  material,  80  that,  while  we  have  in  the  liver  a  large 
general  depot  for  the  temporary  storage  of  glycogen  for  the  use  of  the  body  at 
large,  the  muscular  tissue,  which  is  the  most  active  tissue  of  the  body  from 
a  chemical  standpoint,  is  also  capable  of  laying  up  in  the  form  of  glycogen 
any  excess  of  sugar  brought  to  it.  The  fact  that  glycogen  occurs  so  widely  in 
the  rapidly-growing  tissues  of  embryos  indicates  that  this  glycogenetie  func- 
tion may  at  times  be  exercised  by  any   tissue. 

1  Tebb:  Journal  <;/"  Physiology,  1897  98,  voL  xxii.  }>.  423. 
'-  /..it. thrift fiir  Biologic,  1890,  8.  237. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  33 J 

Conditions  Affecting  the  Supply  of  Glycogen  in  Muscle  and  Liver. — 
In  accordance  with  the  view  given  above  of  the  general  value  of  glycogen — 
namely,  that  it  is  a   temporary  reserve  supply  of  carbohydrate  material  that 
may  be  rapidly  converted  to  sugar  and  oxidized  with  the  liberation  of  energy — 
it  is  found  that  the  supply  of  glycogen  is  greatly  affected  by  conditions  calling  for 
increased  metabolism  in  the  body.    Muscular  exercise  will  quickly  exhaust  the 
supply  of  muscle  and  liver  glycogen,  provided  it  is  not  renewed  by  new  food. 
In  a  starving  animal  glycogen  will  finally  disappear,  except  perhaps  in  traces, 
but  this  disappearance  will  occur  much  sooner  if  the  animal  is  made  to  use  its 
muscles  at  the  same  time.     It  has  been  shown  also  by  Morat  and  Dufourt  that 
if  a  muscle  has  been  made  to  contract  vigorously,  it  will  take  up  much  more 
sugar  from  an  artificial  supply  of  blood  sent  through  it  than  a  similar  muscle 
which  has  been  resting;  on  the  other  hand,  it  has  been  found  that  if  the  nerve 
of  one  leg  is  cut  so  as  to  paralyze  the  muscles  of  that  side  of  the  body,  the  amount 
of  glycogen  will  increase  rapidly  in  these  muscles  as  compared  with  those  of 
the  other  leg,  that  have  been  contracting  meantime  and  using  up  their  glycogen. 
Formation  of  Urea  in  the  Liver. — The  nitrogen  contained  in  the  proteid 
material  of  our  food  is  finally  eliminated,  after  the  metabolism  of  the  proteid 
is  completed,  mainly  in  the  form  of  urea.     As  will  be  explained   in  another 
part  of  this  section,  it  has  been  definitively  proved  that  the  urea  is  not  formed  in 
the  kidneys,  the  organs  that  eliminate   it.     It  has  long  been  considered  a 
matter  of  the  greatest  importance  to  ascertain  in  what  organ  or  tissues  urea  is 
formed.     Investigations  have  gone  so  far  as  to  demonstrate  that  it  arises  in  part 
at  least  in  the  liver;  hence  the  property  of  forming  urea  must  be  added  to  the 
other  important  functions  of  the  liver-cell.     Schroder1  performed  a  number  of 
experiments  in  which  the  liver  was  taken  from  a  freshly-killed  dog  and   irri- 
gated through  its  blood-vessels  by  a  supply  of  blood  obtained    from  another 
dog.     If  the  supply  of  blood  was  taken  from  a  fasting  animal,  then  circulating 
it  through  the  isolated  liver  was  not  accompanied  by  any  increase  in  the  amount 
of  urea  contained  in  it.     If,  on  the  contrary,  the  blood  was  obtained  from  a 
well-fed  dog,  the  amount  of  urea  contained  in  it  was  distinctly  increased   by 
passing  it  through  the  liver,  thus  indicating  that  the  blood  of  an  animal  after 
digestion  contains  something  that    the  liver  can  convert  to  urea.      It  is  to  be 
noted,  moreover,  that   this  power  is  not    possessed   by  all   the  organs,  since 
blood   from  well-fed   animals  showed   no   increase   in    urea  after  being  circu- 
lated through  an  isolated   kidney  or  muscle.      As  further  proof  of  the  area- 
forming  power  of  the  liver  Schroder  found  that  if  ammonium  carbonate  was 
added  to  the  blood  circulating  through  the  liver — to  that  from  the  fasting  as 
well  as  from  the  well-nourished  animal — a  very  decided    increase  in  Hie  urea 
always  followed.      It  follows  from  the  last  experimenl  that  the  liver-cells  arc 
able  to  convert  carbonate  of  ammonium  into  urea.      The  reaction  may  l»c  ex- 
pressed by  the  equation  (MI, ),('()—  2HaO=    CON, II,.     SchondorffMn  some 
later  work  showed  that  if  the  Id 1  of  a  fasting  dog  is  irrigated  through 

1  Archiv fur  experimentelle  Pathologie  und  Pharmakologie,  Bde    xv.  and  xix.,  L882  and  1885. 

2  Pfliiger'a  Archiv  fur  die  gesammtc  Pltysioloi/ir,  is1.):!,  |',(|.  1  i  v.  S.  1'Jii. 


332  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

the  hind  legs  of  a  well-nourished  animal,  no  increase  in  urea  in  the  blood  can 
be  detected  ;  but  if  the  blood,  after  irrigation  through  the  hind  legs,  is  subse- 
quently passed  through  the  liver,  a  marked  increase  in  urea  results.  Obviously, 
the  blood  in  this  experiment  derives  something  from  the  tissues  of  the  leg 
which  the  tissues  themselves  cannot  convert  to  urea,  but  which  the  liver-cells 
can.  Finally,  in  some  remarkable  experiments  upon  dogs  made  by  four  in- 
vestigators (Halm,  Massen,  Nencki,  and  Pawlow),  which  will  be  described 
briefly  in  the  next  section  in  connection  with  urea,  it  was  shown  that  when 
the  liver  is  practically  destroyed  there  is  a  distinct  diminution  in  the  urea 
of  the  urine.  In  birds  uric  acid  takes  the  place  of  urea  as  the  main 
nitrogenous  excretion  of  the  body,  and  Minkowski  has  shown  that  in 
them  removal  of  the  liver  is  followed  by  an  important  diminution 
in  the  amount  of  uric  acid  excreted.  From  experiments  such  as  these 
it  is  safe  to  conclude  that  urea  is  formed  in  the  liver  and  is  then  given  to  the 
blood  and  excreted  by  the  kidney.  When  we  come  to  describe  the  physiological 
history  of  urea  (p.  334  ),  an  account  will  be  given  of  the  views  held  with  regard 
to  the  antecedent  substance  or  substances  from  which  the  liver  produces  urea. 
Physiology  of  the  Spleen. — Much  has  been  said  and  written  about  the 
spleen,  but  we  are  yet  in  the  dark  as  to  the  distinctive  function  or  functions  of 
this  organ.  The  few  facts  that  are  known  may  be  stated  briefly  without  going 
into  the  details  of  theories  that  have  been  offered  at  one  time  or  another. 
The  older  experimenters  demonstrated  that  this  organ  may  be  removed  from 
the  body  without  serious  injury  to  the  animal.  An  increase  in  the  size 
of  the  lymph-glands  and  of  the  bone-marrow  has  been  stated  to  occur  after 
extirpation  ;  but  this  is  denied  by  others,  and,  whether  true  or  not,  it  gives 
but  little  clue  to  the  normal  functions  of  the  spleen.  Laudenbach1  finds  that 
one  result  of  the  removal  of  the  spleen  is  a  marked  diminution  in  the  number 
of  red  corpuscles  and  the  quantity  of  haemoglobin.  He  infers,  therefore,  that  the 
spleen  is  normally  concerned  in  some  way  in  the  formation  of  red  corpuscles. 
These  facts  are  significant,  but  they  need,  perhaps,  further  confirmation.  The 
mosl  definite  facts  known  about  the  spleen  are  in  connection  with  its  move- 
ments. It  has  been  shown  that  there  is  a  slow  expansion  and  contraction  of 
the  organ  synchronous  with  the  digestion  periods.  After  a  meal  the  spleen 
begins  to  increase  in  size,  reaching  a  maximum  at  about  the  fifth  hour,  and 
then  slowly  returns  to  its  previous  size.  This  movement,  the  meaning  of  which 
is  not  known,  i~  probably  due  to  :i  slow  vaso-dilatation,  together,  perhaps,  with! 
a  relaxation  of  the  tonic  contraction  of  the  musculature  of  the  trabecular  In 
addition  to  this  slow  movement,  Roy2  has  shown  that  there  is  a  rhythmic 
contraction  and  relaxation  of  the  organ,  occurring  in  cats  and  dogs  at  intervals 
of  about  one  minute.  Roy  supposes  that  these  contractions  are  effected  through 
the  intrinsic  musculature  of  the  organ — that  is,  the  plain  muscle-tissue  present 
in  the  capsule  and  trabecules — and  he  believes  that  the  contractions  serve  to 
keep  up  a  circulation  through  the  spleen  and  to  make  it<  vascular  supply  more 

1  Centralblatt fiir  Physiologie,  1895,  Bd.  ix.  S.  1. 

2  Journal  of  I'lii/xinl,,,/*/,    1 SS 1 ,  vol.  iii.  p.  203. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  333 

or  less  independent  of  variations  in  general  arterial  pressure.  These  observa- 
tions are  valuable  as  indicating  the  importance  of  the  spleen  functions.  The 
fact  that  there  is  a  special  local  arrangement  for  maintaining  its  circulation 
makes  the  spleen  unique  among  the  organs  of  the  body,  but  no  light  is  thrown 
upon  the  nature  of  the  function  fulfilled.  The  spleen  is  supplied  richly  with 
nerve-fibres  which  when  stimulated  either  directly  or  reflexly  cause  the  organ 
to  diminish  in  volume.  According  to  Schaefer,1  these  fibres  are  contained  in 
the  splanchnic  nerves,  which  carry  also  inhibitory  fibres  whose  stimulation  pro- 
duces a  dilatation  of  the  spleen. 

The  chemical  composition  of  the  spleen  is  complicated  but  suggestive.  Its 
mineral  constituents  are  characterized  by  a  large  percentage  of  iron,  which 
seems  to  be  present  as  an  organic  compound  of  some  kind.  Analysis  shows 
also  the  presence  of  a  number  of  fatty  acids,  fats,  cholesterin,  and,  what  is 
perhaps  more  noteworthy,  a  number  of  nitrogenous  extractives  such  as 
xanthin,  hypoxanthin,  adenin,  guanin,  and  uric  acid.  The  presence  of 
these  bodies  seems  to  indicate  that  active  metabolic  changes  of  some  kind  occur 
in  the  spleen.  As  to  the  theories  of  the  splenic  functions,  the  following  may  be 
mentioned  :  (1)  The  spleen  has  been  supposed  to  give  rise  to  new  red  corpuscles. 
This  it  undoubtedly  does  during  fetal  life  and  shortly  after  birth,  and  in  some 
animals  throughout  life,  but  there  is  no  reliable  evidence  that  the  function  is 
retained  in  adult  life  in  man  or  in  most  of  the  mammals.  (2)  It  has  been 
supposed  to  be  an  organ  for  the  destruction  of  red  corpuscles.  This  view  is 
founded  partly  on  very  unsatisfactory  microscopic  evidence  according  to  which 
certain  large  amoeboid  cells  in  the  spleen  ingest  and  destroy  the  old  red  corpus- 
cles, and  partly  upon  the  fact  that  the  spleen-tissue  seems  to  be  rich  in  an  iron- 
containing  compound.  This  theory  cannot  be  considered  at  present  a-  anything 
more  than  a  suggestion.  (3)  It  has  been  suggested  that  uric  acid  is  pro- 
duced in  the  spleen.  This  substance  is  found  in  the  spleen,  as  stated  above, 
and  it  has  been  shown  by  Horbacewsky  that  the  spleen  contains  a  substance 
from  which  uric  acid  or  xanthin  may  readily  be  formed  ;  but  further  investiga- 
tion lias  shown  that  the  same  substance  is  found  in  lymphoid  tissue  generally. 
If,  therefore,  uric  acid  is  produced  in  the  spleen,  it  is  a  function  of  the  large 
amount  of  lymphoid  tissue  contained  in  it,  and  a  function  which  it  shares  with 
similar  tissues  in  the  rest  of  the  body.  The  lymphoid  tissue  of  the  spleen  must 
also  possess  the  property  of  producing  lymphocytes,  since,  according  to  the  gen- 
eral view,  these  corpuscles  are  formed  in  lymphoid  tissue  generally  wherever 
the  so-called  "  germ-centres  "  occur.  (4)  Lastly,  a  theory  has  been  supported 
by  Schiff  and  Iler/.en,  according  to  which  the  spleen  produces  something  (an 
enzyme)  which,  when  carried  in  the  blood  to  the  pancreas,  acts  upon  the  tryp- 
sinogen  contained  in  this  gland,  converting  it  into  trypsin.  The  experi- 
mental evidence  upon  which  this  view  rests  has  not  been  confirmed  l>v  other 
observers. 

1  Proceedings  of  tin-  Royal  s<,ci<tij,  London,  L896,  vol.  lix.,  No.  355,  and  Journal  <>i'  Physiology. 

1896,  vol.  xx. 


334  AN    AMERICAN    TEXT-HOOK    OF  PHYSIOLOGY. 

G.     The  Kidney  and  the  Skin  as  Excretory  Organs. 

The  secretion  of  the  kidneys  is  the  urine.  The  means  by  which  this  secretion 
is  produced,  it-  relations  to  the  histological  structure  of  the  kidney,  and  its  con- 
nections with  the  blood-  and  nerve-supply  of  that  organ  \\  ill  !><•  found  described 
in  the  section  <>n  Secretion.  In  this  section  will  be  discussed  only  the  chemical 
composition  of  urine,  and  especially  the  physiological  significance  of  itsdiffer- 
em  constituents.  Theurineof  man  isa  yellowish  liquid  varying  greatly  in  depth 
of  color.  It  has  an  average  specific  gravity  of  1020,  and  an  acid  reaction.  The 
acid  reaction  is  not  due  to  a  free  acid,  but  is  usually  attributed  to  an  acid  salt, 
the  acid  phosphate  of  sodium  (Xall.POj).  Under  certain  normal  conditions 
human  urine  may  show  a  neutral  or  even  a  slightly  alkaline  reaction,  especially 
after  meals.  In  fact,  the  reaction  ot*  the  urine  seems  to  depend  directly  on  the 
character  of  the  food.  Among  carnivorous  animals  the  urine  is  uniformly 
acid,  and  among  herbivorous  animals  it  is  uniformly  alkaline,  so  long  as 
they  are  using  a  vegetable  diet,  hut  when  starving  or  wheu  living  upon  the 
mother's  milk — that  is,  whenever  they  are  existing  upon  a  purely  animal  diet — 
the  urine  becomes  acid.  The  explanation,  as  given  by  Drechsel,  is  that  upon 
an  animal  diet  more  acids  are  produced  (from  the  sulphur  and  phosphorus) 
than  the  bases  present  can  neutralize,  whereas  upon  a  vegetable  diet  carbonates 
are  formed  from  the  oxidation  of  the  organic  acids  of  the  food  in  quantities 
sufficient  to  neutralize  the  mineral  acids.  The  chemical  composition  of  urine  is 
very  complex.  Among  the  constituents  constantly  present  under  the  conditions 
of  normal  life  we  have,  in  addition  to  water  and  inorganic  salts,  the  following 
substances:  Urea;  uric  acid;  xanthin ;  creatinin ;  hippuric  acid;  the  urinary 
pigments  (urobilin);  sulphocyanides  in  traces;  acetone;  oxalic  acid,  probably 
as  calcium  oxalate  ;  several  ethereal  sulphuric  acids,  such  as  phenol  and  cresol 
sulphuric  acids,  indoxyl  sulphuric  acid  (indican),  and  skatoxvl  sulphuric  acid; 
aromatic  oxy-acids  ;  some  combinations  of  glycuronic  acid ;  some  representa- 
tives of  the  fatty  acids;  and  dissolved  gases  (X  and  C02).  This  list  would  be 
very  much  extended  if  it  attempted  to  take  in  all  those  substances  occasion- 
ally found  in  the  urine.  The  complexity  of  the  composition  and  the  fact  that 
so  many  different  organic  compounds  occur  or  may  occur  in  small  quantities 
is  readily  understood  when  we  consider  the  nature  of  the  secretion.  Through 
the  kidneys  there  are  eliminated  not  only  what  we  might  call  the  normal  end- 
products  of  the  metabolism  of  the  tissues,  excluding  the  C02,  but  also,  in 
large  part,  the  products  of  decomposition  in  the  alimentary  canal,  the  end- 
products  of  many  organic  substances  occurring  in  our  foods  and  not  usually 
classed  a-  food-stufls,  foreign  substances  introduced  as  drugs,  etc.,  all  of  which 
are  eliminated  either  in  the  form  in  which  they  arc  taken  or  as  derivative 
products  of  some  kind.  "We  shall  speak  briefly  of  the  most  important  of  the 
normal  constituents,  dwelling  especially  upon  their  origin  in  the  body  and  their 
physiological  significance.  For  details  of  chemical  properties  and  reactions, 
reference  musl  be  made  to  the  Chemical  section. 

Urea. — Urea,  which  is  given  the  formula  CH4N20,  is  usually  considered 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  335 

as  an  amide  of  carbonic  acid,   having    therefore  the  structural   formula  of 

C0<  y„-  It  occurs  in  the  urine  in  relatively  large  quantities  (2  per  cent.  -f-). 

As  the  total  quantity  of  urine  secreted  in  twenty-four  hours  by  an  adult  male 
may  he  placed  at  from  1500  to  1700  cubic  centimeters,  it  follows  that  from  30 
to  34  grams  of  urea  are  eliminated  from  the  body  during  this  period  It  is 
the  most  important  of  the  nitrogenous  excreta  of  the  body,  the  end-product 
of  the  physiological  oxidation  of  the  proteids  of  the  body,  and  also  of  the 
albuminoids  when  they  appear  in  the  food.  If  we  know  how  much  urea  is 
secreted  in  a  given  period,  we  know  approximately  how  much  proteid  has 
been  broken  down  in  the  body  in  the  same  time.  In  round  numbers,  1  gram 
of  proteid  will  yield  \  gram  of  urea,  as  may  be  calculated  easily  from  the 
amount  of  nitrogen  contained  in  each.  Since,  however,  some  of  the  nitrogen 
of  proteid  is  eliminated  in  other  forms — uric  acid,  creatinin,  etc. — even  an 
exact  determination  of  all  the  urea  would  not  be  sufficient  to  determine  with 
accuracy  the  total  amount  of  proteid  broken  down.  This  fact  is  arrived  at 
more  perfectly,  as  we  shall  explain  later,  by  a  determination  of  the  total 
nitrogen  of  the  urine  and  other  excretions.  In  addition  to  the  urine,  urea  is 
found  in  slight  quantities  in  other  secretions,  in  milk  (in  traces),  and  in  sweat. 
In  the  latter  liquid  the  quantity  of  urea  in  twenty-four  hours  may  be  quite 
appreciable — as  much,  for  instance,  as  0.8  gram — although  such  a  large  amount 
is  found  only  after  active  exercise.  It  has  been  ascertained  definitely  that  urea 
is  not  formed  by  the  kidneys:  it  is  brought  to  the  kidneys  in  the  blood  for 
elimination,  the  cells  of  the  convoluted  tubules  being  especially  adapted  for 
taking  up  this  material  and  transmitting  it  through  their  substance  to  the 
lumen  of  the  tubules.  That  urea  is  not  made  in  the  kidneys  is  demonstrated 
by  such  facts  as  these:  If  blood,  on  the  one  hand,  is  irrigated  through  an 
isolated  kidney,  no  urea  is  formed,  even  though  substances  (such  as  ammonium 
carbonate)  from  which  urea  is  readily  produced  are  added  to  the  blood;  on  the 
other  hand,  urea  is  constantly  present  in  the  blood  (0.03  18  to  0.1529  per  cent.), 
and  if  the  two  kidneys  are  removed,  it  continues  to  accumulate  steadily  iu  the 
blood  as  long  as  the  animal  survives.  It  has  been  ascertained  that  the  urea  is 
produced  in  part  in  the  liver;  an  account  of  some  of  the  experiments  demon- 
strating this  fact  is  given  on  page  331.  The  most  important  questions  that 
remain  to  be  decided  are,  Through  what  steps  is  the  proteid  molecule  metab- 
olized to  the  form  of  urea?  and,  What  is  the  antecedent  substance  brought 
to  the  liver,  from  which  it  makes  urea?  It  is  impossible  to  answer  these 
questions  perfectly,  but  recent  investigations  have  thrown  a  great  deal  of  light 
on  the  whole  process,  and  they  give  hope  that  before  long  the  entire  history 
of  the  derivation  of  urea  from  proteids  and  albuminoids  will  be  known.  The 
results  of  this  work  may  be  stated  briefly  as  follows: 

1.  Urea  arises  from  proteids  by  a  process  of  hydrolysis  and  oxidation,  with 
the  formation  eventually  of  ammonia  compounds,  which  are  then  conveyed 
to  the  liver  and  there  changed  to  urea.  Drechsel  lias  suggested  that  am- 
monium carbamate  tonus  one  at  least  of  the  ammonia  compounds  that  arc  con- 


336  AN   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

verted  to  urea,  and  gives  the  following  evidence  for  this  view.  In  the 
firsl  place,  Drechsel  found  carbamic  acid  in  the  blood  of  dogs,  and 
Drechsel  and  Abel  have  shown  that  it  occurs  normally  in  the  urine  of 
horses  as  calcium  carbamate  ;  and  Abel  lias  shown  that  it  may  be 
found  in  the  urine  of  dogs  or  infants  after  the  use  of  lime-water.  Drechsel 
has  shown,  further,  that  ammonium  carbamate  may  be  converted  into  urea. 
If  one  compares  the  formulas  of  ammonium  carbamate  ami  urea,  it  is  seen  that 
the  former  may  pass  over  into  the  latter  by  the  loss  of  a  molecule  of  water,  a — 

CO<XI  F-     —  H00  =  CO<XH2. 
OXH,         -  XH2 

Ammonium  carbamate.  Urea. 

Drechsel  supposes,  however,  that  this  dehydration  is  effected  in  an  indirect 
manner;  that  there  is  first  an  oxidation  removing  two  atoms  of  hydrogen, 
and  then  a  reduction  removing  an  atom  of  oxygen.  He  succeeded  in  showing 
that  when  an  aqueous  solution  of  ammonium  carbamate  is  submitted  to  elec- 
trolysis, aud  the  direction  of  the  current  is  changed  repeatedly  so  as  to  get 
alternately  reduction  and  oxidation  processes  at  each  pole,  some  urea  will  be 
produced.  These  facts  show  the  existence  of  ammonium  carbamate  in  the 
body,  and  the  possibility  of  its  conversion  to  urea.  It  remain-  possible, 
however,  that  other  salts  or  compounds  of  ammonia  may  likewise  be  con- 
verted normally  to  urea  by  the  liver,  since  it  has  been  shown  experimentally 
in  artificial  circulation  through  this  organ  that  salts  such  as  ammonium  car- 
bonate, or  even  such  complex  ammonia  compounds  as  leucin  and  glycocoll, 
may  give  rise  to  urea.  Experiments  made  by  Halm.  Pawlow,  Massen, 
and  Nencki  '  show  that  in  dogs  removal  of  the  liver  is  followed  by  a 
decrease  in  the  amount  of  urea  in  the  urine  and  an  increase  in  the 
ammonia  contents.  In  these  remarkable  experiments  a  fistula  was 
made  between  the  portal  vein  and  the  inferior  vena  cava,  the  result  of  which 
was  that  the  whole  portal  circulation  of  the  liver  was  abolished,  and  the  only 
blood  that  the  organ  received  was  through  the  hepatic  artery.  If,  now,  this 
artery  was  ligated  or  the  liver  was  cut  away,  as  was  done  in  some  of  the  ex- 
periments, then  the  result  was  practically  an  extirpation  of  the  entire  organ — an 
operation  which  has  always  been  thought  to  be  impossible  with  mammals.  The 
animals  in  these  investigations  survived  this  operation  for  some  time,  but  they 
died  finally,  showing  a  series  of  symptoms  which  indicated  a  deep  disturbance 
of  tin'  nervous  system.  It  was  found  that  the  symptoms  of  poisoning  in  these 
animals  could  be  brought  on  before  they  developed  spontaneously  by  feeding 
the  dogs  upon  ;i  rich  meat  diet,  or  with  .-alts  of  ammonia  or  carbamic  acid.  Later 
investigations 2  showed  that  in  normal  animals  the  ammonia  contents  of  the 
blood  in  the  portal  vein  are  from  three  to  four  times  what  is  found  in  the  arte- 
rial blood,  but  that  after  the  operation  described  the  ammonia  in  the  arterial 
blood    increases  and  at  the  time  of  the   development  of  the   fatal   symptoms 

1  Ardiir  far  experimentelle  Pathologie  and  Pharmakolor/ie,  1893,  Bd.  xxxii.  S.  161. 

2  Nenoki,  Pawlow,  and  Zaleski :    Ibid.,  1895,    Bd.  xxxvii.  S.  26;  also,  Xencki  and  Pawlow: 
Archives  '/•.-•  Sciences  biologiques,  t.  5,  p.  213. 


CHEMISTRY  OF  DIGESTION   AND    NUTRITION.  337 

reaches  about  the  percentage  which  is  normal  to  the  blood  of  the  portal  vein. 
It  would  seem  from  these  investigations  that  the  liver  stands  between  the 
portal  circulation  and  the  general  systemic  circulation  and  protects  the  latter 
from  the  comparatively  large  amount  of  ammonia  compounds  contained  in  the 
portal  blood  by  converting  these  compounds  to  urea.  If  the  liver  is  thrown 
out  of  function,  ammonia  compounds  accumulate  in  the  blood  and  cause 
death.  The  rich  amount  of  ammonia  in  the  portal  blood  seems  to  come 
chiefly  from  the  decomposition  of  proteid  material  in  the  glands  of  the 
stomach  and  pancreas  during  secretion.  Similar  ammonia  salts  are  probably 
formed  in  other  active  proteid  tissues,  since  the  percentage  of  ammonia  in  the 
tissues  is  considerably  greater  than  in  the  blood,  and  these  compounds  also  are 
doubtless  converted  to  urea  in  the  liver,  in  part  at  least.  As  to  the  origin  of 
the  ammonia  compounds  there  is  little  direct  evidence.  They  come  in  the  long 
run,  of  course,  from  the  nitrogenous  food-stuffs,  proteids  and  albuminoids. 
Drechsel,  having  reference  to  one  form  only,  namely,  ammonium  carbamate, 
supposes  that  the  proteids  first  undergo  hydrolytic  cleavage,  with  the  formation 
of  amido-  bodies,  such  as  leucin,  tyrosin,  aspartic  acid,  glycocoll,  etc.;  that 
these  bodies  undergo  oxidation  in  the  tissues,  with  the  formation  of 
NH3,  C02,  and  H20  ;  and  that  the  XH:j  and  CG2  then  unite  synthetically  to 
form  ammonium  carbamate,  which  is  carried  to  the  liver  and  changed  to 
urea.  There  is  reason  to  believe  that  the  formation  of  ammonia  compounds 
takes  place  in  the  tissues  generally. 

2.  Even  after  the  removal  of  the  liver  some  urea  is  still  found  in  the  urine. 
This  fact  proves  that  other  organs  are  capable  of  producing  urea,  but  what  the 
other  organs  are  and  by  what  process  they  make  urea  are  points  yet  undeter- 
mined. It  seems  probable  that  some  of  the  ammonia  compounds  which  are 
now  known  to  be  formed  in  the  tissues  generally  and  to  be  given  off  to  the 
blood  may  be  converted  into  urea  elsewhere  than  in  the  liver.  Just  as  the 
glycogenic  function  of  the  liver-cells  is  shared  to  a  less  extent  by  other  tis- 
sues— e.  g.  the  muscle-fibres — it  is  possible  that  their  power  of  converting 
ammonia  salts  to  urea  may  be  possessed  to  a  lesser  degree  by  other  cell-,  and 
for  this  reason  removal  of  the  liver  is  not  followed  at  once  by  a  fatal  result. 
Concerning  this  point,  however,  we  must  wait  for  further  investigation. 
Drechsel  has  recently  called  attention  to  a  method  of  obtaining  urea  directly 
from  proteid  outside  of  the  body.  Mis  method  is  interesting  not  only 
because  it  is  the  first  laboratory  method  discovered  of  producing  urea  from 
proteid,  but  also  because  it  is  possible  that  substantially  the  same  process  may 
occur  inside  the  body.  The  method  consists,  in  brief,  in  fust  boiling  the  pro- 
teid with  an  acid;  IIC1  was  used,  together  with  some  metallic  zinc,  so  ;i-  to 
keep  up  a  constant  evolution  of  hydrogen  and  to  exclude  atmospheric  oxygen. 
Among  the  products  of  decomposition  of  the  proteid  thus  produced  was  a 
substance  termed  lysatinin  (C6HuNsO),  and  when  this  body  was  isolated  and 
treated  with  boiling  baryta-water  (Ba(OH)2)  some  urea  was  obtained.  It  is  to 
be  noted  that  in  this  case  the  urea  was  obtained  not  by  the  oxidation  of  the 
proteid,  but  by  a  series  of  decompositions  or  cleavages  of  the  proteid  molecule. 
Vol.  I.— 22 


338  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

Now,  lysatinin  occurs  also  in  the  body  as  one  of  the  products  of  the  con- 
tinued action  of  trypsin  on  proteids (see p. 303).  It  is  possible,  therefore,  that 
by  further  hydrolysis  this  substance,  when  it  occurs,  is  converted  to  urea,  and 
that  normally  a  part  of  the  urea  arises  from  proteids  by  this  process. 

Uric  Acid  and  Xanthin  Bodies. — Uric  acid,  which  has  the  formula 
CgH4X403,  is  found  constantly,  but  in  relatively  small  quantities,  in  human 
urine  and  in  the  urine  of  mammals  generally.  The  total  quantity  in  the  urine  of 
man  under  normal  conditions  varies  from  0.2  to  1  gram  every  twenty-four  hours. 
In  the  urine  of  birds  and  reptiles  it  forms  the  chief  nitrogenous  constituent.  In 
these  animals  it  takes  the  place  physiologically  of  urea  in  mammalia  in  that  it 
represents  the  main  end-product  of  the  metabolism  of  the  proteids  in  the  body. 
It  i»  evident  that  at  some  point  in  the  process  the  metabolism  of  the  proteids 
in  mammalia  differs  from  that  in  birds  and  reptiles,  since  in  the  one  urea, 
and  in  the  other  uric  acid,  is  the  outcome.  Uric  acid  occurs  in  such  small 
quantities  in  mammals  that  its  place  of  origin  has  been  investigated  with  dif- 
ficulty. Among  birds  and  reptiles  uric  acid  represents  the  chief  nitrogenous 
excretion  of  the  urine,  taking  the  place  physiologically  of  urea  in  the  mam- 
malia. As  in  the  case  of  urea,  it  has  been  shown  that  in  birds  uric  acid 
originates  in  the  liver.  Extirpation  of  the  kidneys  in  these  animals  leads 
to  an  accumulation  of  uric  acid  in  the  blood  and  tissues.  Removal  of 
the  liver,  on  the  contrary,  causes  a  decrease  in  the  excretion  of  uric  acid  and 
an  increase  in  the  ammonia  contents  of  the  urine.  It  may  be  concluded, 
therefore,  that  in  birds  uric  acid  is  formed  in  part  in  the  liver  from  ammonia 
compounds  (ammonium  lactate).  Reasoning  from  analogy,  we  should  sup- 
pose that  in  the  mammalia  uric  acid  has  a  similar  origin,  but  experiments 
fail  to  support  this  view.  When  a  mammal  is  fed  with  ammonium  lactate 
or  urea  there  is  no  increase  in  the  excretion  of  uric  acid.  Within  recent 
years  a  new  hypothesis  has  been  advanced  by  Horbacewsky,  and  consider- 
able experimental  evidence  has  since  given  material  support  to  his  views.1 
According  to  Horbacewsky,  uric  acid  may  be  regarded  as  a  specific  end- 
product  of  the  nucleins  contained  in  the  nuclei  of  cells,  and  is  formed  by  an 
oxidation  of  a  grouping  in  the  nuclein  which  may  also  give  rise  to  other 
members  of  the  class  of  so-called  alloxuric  bases,  such  as  xanthin,  hypo- 
xanthin,  or  adenin.  Feeding  a  man  with  food  rich  in  nucleins — the  thymus 
gland,  for  instance — leads  to  a  marked  increase  in  the  excretion  of  uric  acid, 
and  feeding  with  one,  at  least,  of  the  alloxuric  bases,  hypoxanthin,  gives  a 
similar  result.  On  this  view  uric  acid  should  give  an  indication  of  the 
extent  of  the  katabolism  or  disintegration  of  the  cell-nuclei,  especially 
perhaps  in  the  lymphoid  tissue.  It  is  probable,  however,  that  the  actual 
amount  of  uric  acid  excreted  in  the  urine  does  not  represent  truly  the  entire 
amount  formed  in  the  body.  When  uric  acid  is  fed  to  an  animal  it  does  not 
all  reappear  in  the  urine,  indicating  that  this  substance  may  undergo  metab- 
olism in  the  body  to  a  limited  extent,  its  nitrogen  appearing  probably  as 
urea.  Possibly,  therefore,  some  of  the  uric  acid  normally  produced  in  the 
body  undergoes  a  similar  fate,  only  a  portion  escaping  in  the  urine. 

1  Minkowski :  Archivfur  ezperimenteUe  Pathologie  wnd  Pharmakoloffie,  Bd.  41,  S.  375. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  339 

Xanthin  (C5H4N402),  hypoxanthin  (C5H4N40),  guanin  (C5H4N4ONH), 
and  adenin  (C5H4N4NH)  arc  substances  closely  related  to  uric  acid,  and  are 
found  in  traces  in  the  urine.  Since  they  also  originate  in  the  disintegration 
of  nucleins,  it  is  probable  that  their  physiological  significance  is  the  same  as 
that  of  uric  acid,  and  that  to  the  extent  to  which  they  occur  they  also  repre- 
sent an  end-product  of  the  katabolism  of  cell-nuclei.  These  bodies  are 
found  in  greatest  quantity  in  muscle,  and  are  present,  therefore,  in  meat- 
extracts.  It  is  interesting  in  this  connection  to  call  attention  to  the  fact  that 
theobromin  (dimethyl-xanthin)  and  caffein  (trimethyl-xanthin)  are  closely 
related  to  the  xanthin  bodies. 

Creatinin. — Creatinin  (C4H7XhO)  is  a  crystalline  nitrogenous  substance 
constantly  found  in  urine.  It  is  closely  related  to  creatin  (C4H9N302),  the  two 
substances  differing  by  a  molecule  of  water;  the  creatin  changes  to  creatinin 
upon  heating  with  mineral  acids.  Creatinin  occurs  in  urine  to  the  extent 
of  about  1.12  grams  per  day  in  man.  In  dogs  it  has  been  found  that 
the  amount  may  vary  between  0.5  and  4.9  grams  per  day  according  to 
the  diet,  an  increase  in  the  amount  of  meat  in  the  diet  causing  an  increase 
in  the  creatinin.  This  is  readily  explained  by  the  fact  that  creatin  is  a 
constant  constituent  of  muscle,  and  when  taken  into  the  stomach  it  is 
eliminated  in  the  urine  as  creatinin.  It  is  evident,  therefore,  that  part 
of  the  creatinin  of  the  urine  is  derived  from  the  meat  eaten,  and  does 
not  represent  a  metabolism  within  the  body.  A  part,  however,  comes 
undoubtedly  from  the  destruction  of  proteid  within  the  body.  In  this  con- 
nection the  following  facts  are  suggestive  and  worthy  of  consideration,  although 
they  cannot  be  explained  satisfactorily :  The  mass  of  proteid  tissue  in  the  body 
is  found  in  the  muscles,  and  the  end-product  of  the  destructive  metabolism  of 
proteid  is  supposed  to  be  chiefly  urea.  Nevertheless,  urea  is  not  found  in  the 
muscles,  while  creatin  occurs  in  considerable  quantities,  as  much  as  90  grains 
being  contained  in  the  body-musculature  at  any  one  time.  Only  a  small 
quantity  (1.12  grams)  of  creatin  is  eliminated  in  the  urine  as  creatinin  during 
a  day.  What  becomes  of  the  relatively  large  quantity  of  creatin  in  the  mus- 
cles? It  has  been  suggested  that  it  is  one  of  the  precursors  of  urea — that  it 
represents  an  end-product  of  the  proteid  destroyed  in  muscle  which  is  subse- 
quently converted  to  urea  in  the  liver  or  elsewhere.  This  supposition  is  sup- 
ported by  the  fact  that  creatin  may  be  decomposed  readily  in  the  laboratory, 
with  the  formation  of  urea  among  other  products.  But  against  this  theory 
we  have  the  important  fact  that  creatin  introduced  into  the  blood  is  not  con- 
verted to  urea,  but   is  eliminated  as  creatinin. 

Hippuric  Acid. — This  substance  has  the  formula  C9H9N03.  Its  molecular 
structure  is  known,  since  upon  decomposition  it  yields  benzoic  acid  and  gly- 
cocoll,  and,  moreover,  it  may  be  produced  synthetically  by  the  union  of  these 
two  substances.  Hippuric  acid  may  be  described,  therefore,  as  a  benzoyl-amido- 
acetic  acid.  It  is  found  in  considerable  quantities  in  the  urine  of  herbivorous 
animals  (1.5  to  2.5  per  cent.),  and  in  much  smaller  amounts  in  the  urine  of 
man  and  of  the  earnivora.      In   human  urine,  on  an  average  diet,  about  0.7 


340  -I.V    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

gram  is  excreted  in  twenty-tour  hours.  If,  however,  the  diet  is  largely 
table,  tli is  amount  may  be  increased  greatly.  These  last  facts  are  readily 
explained.  It  has  been  found  that  if  benzoic  acid  or  related  substances  con- 
taining this  group  are  fed  to  animals,  they  appear  in  the  mine  as  hippuric 
acid.  Evidently,  a  synthesis  has  taken  place  within  the  body,  and  Bunge  and 
Schmiedeberg  proved  conclusively  that  in  dogs,  and  probably,  therefore,  in 
man,  the  union  of  the  benzoic  acid  to  glycocoll  occurs  mainly  in  the  kidney 
itself.  We  can  understand,  therefore,  why  vegetable  foods  which  are  known  to 
contain  substances  belonging  to  the  aromatic  series  and  yielding  benzoic  acid 
should  increase  the  output  of  hippuric  acid  in  the  urine.  Since,  however,  in 
starving  animals  or  in  animals  \\<\  entirely  on  meat  hippuric  acid  is  still  pres- 
ent, although  reduced  in  amount,  it  follows  that  it  arises  in  part  as  one  of  the 
results  of  body-metabolism.  Among  the  various  products  of  the  breaking- 
down  of  the  proteid  molecule,  it  is  probable  that  some  benzoic  acid  occurs, 
and,  if  so,  it  is  excreted  in  combination  with  glycocoll  as  hippuric  acid.  It 
should  lie  added,  finally,  that  some  of  the  hippuric  acid  is  supposed  to  be  de- 
rived from  the  process  of  proteid  putrefaction  that  occurs  to  a  greater  or 
less  extent  in  the  large  intestine. 

Conjugated  Sulphates. — A  good  part  of  the  sulphur  eliminated  in  the 
urine  is  in  the  form  of  ethereal  salts  with  organic  compounds  of  the  aromatic 
and  indigo  series.  Quite  a  number  of  these  compounds  have  been  described  ; 
the  most  important  are  the  compounds  with  phenol  (C6H5OS02OH),  cresol 
(C7H7O.S02OH),  indol  (CsH6XOS02OH),  and  skatol  (C9H8XOS02OH). 
These  four  substances,  phenol,  cresol,  indol,  and  skatol,  are  formed  in  the  in- 
testine during  the  process  of  putrefactive  decomposition  of  the  proteids  (p.  310). 
They  are  produced  in  small  quantities,  and  they  may  be  excreted  in  part  in 
the  feces,  but  in  part  they  are  absorbed  into  the  blood.  They  are  in  them- 
selves injurious  substances,  but  it  is  supposed  that  in  passing  through  the 
liver — which  must  of  necessity  happen  before  they  get  into  the  general  cir- 
culation— they  are  synthetically  combined  with  sulphuric  acid,  making  the 
so-called  "conjugated  sulphates,"  which  are  harmless,  and  which  are  event- 
ually excreted  by  the  kidneys. 

Water  and  Inorganic  Salts. —  Water  is  lost  from  the  body  through  three 
main  channels — namely,  the  lungs,  the  skin,  and  the  kidney,  the  last  of  these 
being  the  most  important.  The  quantity  of  water  lost  through  the  lungs 
probably  varies  within  small  limits  only.  The  quantity  lost  through  the 
sweat  varies,  of  course,  with  the  temperature,  with  exercise,  etc.,  and  it  may 
be  said  that  the  amounts  of  water  secreted  through  kidney  and  skin  stand  in 
something  of  an  inverse  proportion  to  each  other;  that  is,  the  greater  the 
quantity  lost  through  the  skin,  the  less  will  be  secreted  by  the  kidneys. 
Through  these  three  organs,  but  mainly  through  the  kidneys,  the  blood  is 
being  continually  depleted  of  water,  and  the  loss  must  be  made  up  by  the 
ingestion  of  new  water.  When  water  is  swallowed  in  excess  the  superfluous 
amount  is  rapidly  eliminated    through   the   kidneys.     The  amount  of  water 


CHEMISTRY   OF  DIGESTION  AND    NUTRITION.  341 

secreted  may  be  increased  by  the  action  of  diuretics,  such  as  potassium  nitrate 
and  caffein. 

Tin1  inorganic  suits  of  urine  consist  chiefly  of  the  chlorides,  phosphates, 
and  sulphates  of  the  alkalies  and  the  alkaline  earths.  It  may  be  said  in 
general  that  they  arise  partly  from  the  salts  ingested  with  the  food,  which 
salts  are  eliminated  from  the  Mood  by  the  kidney  in  the  water-secretion,  and 
in  part  they  are  formed  in  the  destructive  metabolism  thai  takes  place  in  the 
body,  particularly  that  involving  the  proteids  and  related  bodies.  Sodium 
chloride  occurs  in  the  largest  quantities,  averaging  about  1  5  grams  per  day,  of 
which  the  larger  part,  doubtless,  is  derived  directly  from  the -alt  taken  in  the 
food.  The  phosphates  occur  in  combination  with  Ca  and  Mg,  but  chiefly  as 
the  acid  phosphates  of  Xa  or  K.  The  acid  reaction  of  the  urine  is  usually 
attributed  to  these  latter  substances.  The  phosphates  result  in  part  from  the 
destruction  of  phosphorus-containing  tissues  in  the  body,  but  chiefly  from 
the  phosphates  of  the  food.  The  sulphates  of  urine  are  found  partly  in  an 
oxidized  form  as  simple  sulphates  or  conjugated  with  organic  compounds,  as 
described  above,  and  in  small  part  in  a  neutral  or  unoxidized  form,  such  as 
potassium  sulphocyanide,  or  ethyl-sulphide,  (C2H5)2S.  The  total  quantity  of 
sulphuric  acid  eliminated  is  estimated  to  average  about  2.5  grams  per  day. 
Sulphur  constitutes  a  constant  element  of  the  proteid  molecule,  and  the  quan- 
tity of  it  eliminated  in  the  urine  may  be  used,  as  in  the  ease  of  nitrogen,  to 
determine  the  total  destruction  of  proteid  within  a  given  period. 

Functions  of  the  Skin. — The  physiological  activities  of  the  skin  are 
varied.  It  forms,  in  the  first  place,  a  sensory  surface  covering  the  body,  and 
interposed,  as  it  were,  between  the  external  world  and  the  inner  mechanism. 
Nerve-fibres  of  pressure,  temperature,  and  pain  are  distributed  over  its  sur- 
face, and  by  means  of  these  fibres  reflexes  of  various  kinds  are  effected  which 
keep  the  body  adapted  to  changes  in  its  environment.  The  physiology  of  the 
skin  from  this  standpoint  is  discussed  in  the  section  on  Cutaneous  Sensations. 
Again,  the  skin  plays  a  part  of  immense  value  to  the  body  in  regulating  the 
body-temperature.  This  regulation,  which  is  effected  by  variations  in  the 
blood-supply  or  the  sweat-secretion,  is  described  at  appropriate  places  in  the 
sections  on  Animal  Heat,  Circulation,  and  Secretion.  In  the  female,  during 
the  period  of  lactation,  the  mammary  glands,  which  must  be  reckoned  aiming 
the  organs  of  the  skin,  form  an  important  secretion,  the  milk  ;  the  physiology 
of  this  gland  is  described  in  the  sections  on  Secretion  ami  Reproduction.  In  this 
section  we  are  concerned  with  the  physiology  of  the  skin  from  a  different  stand- 
point— namely,  as  an  excretory  organ.  The  excretions  of  the  -kin  are  formed 
in  the  sweat-glands  and  the  sebaceous  glands.  The  sweat-glands  arc  distrib- 
uted  more  or  less  thickly  over  the  entire  surface  of  the  body,  with  the  excep- 
tion of  the  prepuce  and  glans  penis,  while  the  sebaceous  glands,  usually  in  ( - 

Election  with  the  hairs,  are  also  found  everywhere  except   upon  the   palms  of 
the  hands  and  the  soles  of  the  feet. 

Sweat. — Sweat,  or  perspiration,  which  is  the  secretion  of  the  sweat-glands, 
is  a  colorless  liquid  with  a  peculiar  odor  and  a  salty  taste.      Its  specific  gravity 


342  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

is  given  at  1004,  and  in  man  it  usually  has  an  acid  reaction.  As  can  readily  be 
understood,  the  quantity  secreted  in  twenty-four  hours  varies  greatly,  the  secre- 
tion being  influenced  by  variations  in  temperature,  by  exercise,  and  by  psychical 
and  pathological  conditions;  an  average  estimate  places  the  daily  secretion  at 
from  700  to  900  grams.  Chemically,  the  secretion  consists  of  water  and  inor- 
ganic salts,  traces  of  fats,  fatty  acid,  eholesterin,  and  urea.  Of  the  inorganic 
salts,  Nad  is  by  far  the  most  abundant:  it  occurs  in  quantities  varying  from 
2  to  3.5  parts  per  thousand.  The  elements  of  the  sweat  which  are  of  import- 
ance from  an  excretory  standpoint  are  water,  inorganic  salts,  and  urea  or  related 
nitrogenous  compounds.  As  was  said  above,  sweat  constitutes  the  second  in 
importance  of  the  three  main  channels  through  which  water  is  lost  from  the 
body.  The  quantity  eliminated  in  the  sweat  is  to  a  certain  extent  inversely 
proportional  to  that  secreted  by  the  kidneys;  but  the  physiological  value  of 
the  secretion  of  water  by  the  sweat-glands  seems  to  lie  not  so  much  in  the  fact 
that  it  is  necessary  in  maintaining  the  water-equilibrium  of  the  blood  and  tis- 
sues as  in  the  important  part  it  takes  in  controlling  the  heat-loss  from  the  skin: 
the  greater  the  evaporation  of  sweat,  the  greater  the  loss  of  heat.  The  urea  is 
described  as  occurring  in  traces.  As  far  as  it  occurs,  it  represents,  of  course,  so 
much  proteid  destroyed,  but  usually  in  calculating  the  proteid  loss  of  the  body 
this  element  has  been  neglected.  Argutinsky  demonstrated,  however,  that  in 
special  cases — namely,  during  periods  of  unusual  muscular  work  or  after  vapor- 
baths — the  total  weight  of  nitrogen  eliminated  by  the  skin  may  be  of  consider- 
able importance,  amounting  to  as  much  as  0.7  to  0.8  gram.  Under  ordinary 
circumstances  the  excretion  of  urea  and  related  compounds  through  the  skin 
must  be  regarded  as  of  very  subsidiary  importance,  but  the  amount  may  be 
increased  markedly  under  pathological  conditions. 

Sebaceous  Secretion. — The  sebaceous  secretion  is  an  oily,  semi-liquid 
material,  the  quantity  of  which  cannot  be  estimated  even  approximately. 
Chemically,  it  consists  of  water  and  salts,  albumin  and  epithelium,  fats  and 
fatty  acids.  Its  excretory  importance  in  connection  with  the  metabolism  of 
the  body  must  be  slight.  Its  chief  physiological  value  must  be  sought  in 
its  effect  upon  the  hairs,  which  are  kept  oiled  and  pliant  by  the  secretion. 
Moreover,  it  forms  a  thin,  oily  layer  over  most  of  the  surface  of  the 
skin ;  and  we  may  suppose  that  this  layer  of  oil  is  of  value  in  two 
ways — in  preventing  too  great  a  loss  of  water  through  the  skin,  and  in 
offering  an  obstacle  to  the  absorption  of  aqueous  solutions  brought  into 
contact  with  the  skin. 

Excretion  of  C02. — In  some  of  the  lower  animals — the  frog,  for  ex- 
ample— the  skin  takes  an  important  part  in  the  respiratory  exchanges,  elim- 
inating C02  and  absorbing  O.  In  man,  and  presumably  in  the  mammalia 
generally,  it  has  been  ascertained  that  changes  of  this  kind  are  very  slight. 
Estimates  of  the  amount  of  C02  given  off  from  the  skin  of  man  during 
twenty-four  hours  vary  greatly,  but  the  amount  is  small,  and  is  certainly  less 
than  one  one-hundredth  part  of  the  amount  given  off'  through  the  lungs. 


CHEMISTRY  OF  DIGESTION  AND    NUTRITION.  343 

H.  Body-metabolism  ;  Nutritive  Value  of  the  Food-stuffs. 

Determination  of  Total  Metabolism. — We  have  so  far  studied  the 
changes  that  the  food-stuffs  undergo  during  digestion,  the  form  in  which  they 
are  absorbed  into  the  blood,  their  history  in  the  tissues  to  some  extent,  and  the 
final  condition  in  which,  after  being  decomposed  in  the  body,  they  are  eliminated 
in  the  excreta.  To  ascertain  the  true  nutritional  value  of  the  food-stuffs  it 
is  of  the  utmost  importance  that  we  should  have  some  means  of  estimating 
accurately  the  kind  and  the  amount  of  body-metabolism  during  a  given  period 
in  relation  to  the  character  of  the  diet  used.  Fortunately,  this  end  may  be 
reached  by  a  careful  study  of  the  excreta.  The  methods  employed  can  readily 
be  understood  in  principle  from  a  brief  description.  It  has  been  made  suf- 
ficiently clear  before  this,  perhaps,  that  by  determining  the  total  amount  of  the 
nitrogenous  excreta  we  can  reckon  back  to  the  amount  of  proteid  (or  albu- 
minoid) destroyed  in  the  body.  In  the  case  of  proteids  or  albuminoids  that 
undergo  physiological  oxidation  all  the  nitrogen  appears  in  the  forms  of  urea, 
uric  acid,  creatinin,  xanthin,  etc.,  which  are  eliminated  mainly  through  the  urine, 
and  may  therefore  be  collected  and  determined.  The  following  practical  facts 
are,  however,  to  be  borne  in  mind  in  this  connection  :  The  nitrogenous  excre- 
tion of  the  urine  is  mainly  in  the  form  of  urea  which  can  be  estimated  as  such, 
but  it  is  much  more  accurate  to  determine  the  total  nitrogen  in  the  urine  during 
a  given  period,  using  some  one  of  the  approved  methods  for  nitrogen-deter- 
mination, and  to  calculate  back  from  the  amount  of  nitrogen  to  the  amount  of 
proteid.  By  this  means  all  the  nitrogenous  excreta  which  may  occur  in  the 
urine  are  allowed  for ;  and  since  the  various  proteids  differ  but  little  in  the 
amount  of  nitrogen  which  they  contain,  the  average  being  from  15.5  to  16  per 
cent.,  it  is  only  necessary  to  multiply  the  total  quantity  of  nitrogen  found  in  the 
excretions  by  6.25  (proteid  molecule  :  N  ::  100  :  16)  to  ascertain  the  amount  of 
proteid  destroyed.  In  accurate  calculations  it  is  necessary  to  determine  the  total 
nitrogen  in  the  feces  as  well  as  in  the  urine,  and  for  two  reasons:  first,  in  ordi- 
nary diets  of  some  vegetable  and  animal  proteid  they  may  escape  digestion 
and  this  amount  must  be  determined  and  deducted  from  the  total  proteid  eaten 
in  order  to  ascertain  what  nitrogenous  material  has  actually  been  taken  into  the 
body;  second,  the  secretions  of  the  alimentary  canal  contain  a  certain  quan- 
tity of  nitrogenous  material,  which  represents  a  genuine  excretion,  and  should 
be  included  in  estimates  of  the  total  proteid-destruction.  Recent  work 
seems  to  show  that  in  ordinary  diets  most  of  the  nitrogen  of  the  feces  has 
the  latter  origin.  The  nitrogen  eliminated  as  urea,  etc.,  in  the  sweat,  milk, 
and  saliva  is  neglected  under  ordinary  circumstances  because  the  amount  is 
too  small  to  affect  materially  any  calculations  made.  To  determine  the  total 
amount  of  non-nitrogenous  material  destroyed  in  the  body  during  a  given 
period,  two  data  are  required:  first,  the  total  nitrogen  in  the  excreta  of  the 
body;  second,  the  total  amount  of  carbon  given  oil'  from  the  lungs  and  in  the 
various  excreta.  From  the  total  nitrogen  one  calculates  how  much  proteid  was 
destroyed,  and,  deducting  from  the  total  carbon  the  amount  corresponding  to 


341  .4.V    AMERICAN    TEXT-HOOK    OF   PHYSIOLOGY. 

tliis  quantity  of  proteid,  what  remains  represents  the  carboD  derived  from  the 
metabolism  of  the  non-nitrogenous  material — that  is,  from  the  fat  or  carbo- 
hydrate. By  methods  of  this  kind  it  is  possible  to  reckon  back  from  the 
excreta  to  the  total  amount  of  material,  consisting  of  proteid,  fat,  and  carbo- 
hydrate, which  lias  been  consumed  in  the  body  within  a  certain  period.  If,  now, 
by  analyzing  the  food  or  by  making  use  of  analyses  already  made  (see  p.  278),  one 
determines  how  great  a  quantity  of  proteid,  fat,  and  carbohydrate  has  been  taken 
into  the  body  in  the  same  period,  then,  by  comparison  of  the  total  ingesta  and 
egesta,  it  is  possible  to  strike  a  balance  and  to  determine  whether  all  the  proteid, 
fat.  and  carbohydrate  of  the  food  have  been  destroyed,  or  whether  some  of  the 
food  has  been  stored  in  the  body,  and  in  this  case  whether  it  is  nitrogenous  or 
non-nitrogenous  material,  or,  lastly,  whether  some  of  the  reserve  material  of 
the  body,  nitrogenous  or  non-nitrogenous,  has  been  destroyed  in  addition  to 
the  supply  of  food.  It  is  needless  to  remark  that  "  balance  experiments"  of 
this  character  are  very  laborious,  particularly  as  they  must  be  made  over  long 
intervals — one  or  more  days.  Nevertheless,  a  great  deal  of  work  of  this 
kind  has  been  done  upon  man  as  well  as  upon  lower  animals,  especially  by 
Voit '  and  Pettenkofer.  In  the  experiments  upon  man  the  urine  and  feces 
were,  collected  carefully  and  the  total  nitrogen  was  determined  ;  at  the  same  time 
the  total  quantity  of  C02  given  off  from  the  lungs  was  estimated  for  the  entire 
period.  The  determination  of  the  C02  was  made  possible  by  keeping  the  man 
in  a  specially-constructed  chamber  through  which  air  was  drawn  by  means  of  a 
pump;  the  total  quantity  of  air  drawn  through  was  indicated  by  a  gasometer, 
and  a  measured  portion  of  this  air  was  drawn  off  through  a  separate  gasometer 
and  was  analyzed  for  its  C02.  It  was  found  that  the  method  is  practicable :  that 
by  the  means  described  a  nearly  perfect  balance  may  be  struck  between  the  income 
and  the  outgo  of  the  body.  Experiments  of  this  general  character  have  been 
used  to  determine  the  fate  of  the  food-stuffs  in  the  body  under  different  con- 
ditions, the  essential  part  that  each  food-stuff  takes  in  general  nutrition,  and 
so  on.  In  this  and  the  succeeding  sections  we  shall  have  to  consider  some  of 
the  main  results  obtained  ;  but  first  it  will  be  convenient  to  define  two  terms 
frequently  used  in  this  connection — namely,  "  nitrogen  equilibrium "  and 
"  carbon  equilibrium." 

Nitrogen  Equilibrium. — By  "nitrogen  equilibrium"  we  mean  that  condition 
of  an  animal  in  which,  within  a  definite  period,  the  nitrogen  of  the  excreta  is 
equal  in  amount  to  the  nitrogen  of  the  food  ;  in  other  words,  that  condition 
in  which  the  proteid  (and  albuminoid)  food  eaten  exactly  covers  the  loss  of 
proteid  (and  albuminoid)  in  the  body  during  the  same  time.  W  an  animal 
is  giving  off  more  nitrogen  in  its  excreta  than  it  receives  in  its  food,  then 
the  animal  must  be  losing  proteid  from  its  body;  if,  on  the  contrary,  the  food 
that  it  eats  contains  more  nitrogen  than  is  found  in  the  excreta,  the  animal  must 
oe  storing  proteid  in  its  body.  A  condition  of  nitrogen  equilibrium  is  the 
normal  state  of  a  properly-nourished  adult.  It  is  important  to  remember  that 
nitrogen  equilibrium  may  be  maintained  at  different  levels;  that  is,  one  may 
'  Hermann'*  Handiuch  der  Physwlogie,  18S1,  lid.  vi. 


CHEMISTRY   OF  DIGESTION  AND    NUTRITION.  345 

begin  with  a  starving  animal  and  slowly  increase  the  amount  of  nitrogenous  food 
until  nitrogen  equilibrium  is  just  established.  If  now  the  amount  of  nitrog- 
enous food  is  increased — say  doubled — the  excess  does  not,  of  course,  continue 
to  be  stored  up  in  the  animal's  body;  on  the  contrary,  in  a  short  time  the 
amount  of  proteid  destroyed  in  the  body  will  be  increased  to  such  an  extent 
that  nitrogen  equilibrium  will  again  be  established  at  a  higher  level,  the  animal 
in  this  case  eating  more  and  destroying  more.  The  highest  limit  at  which  nitro- 
gen equilibrium  can  be  maintained  is  determined,  apparently,  by  the  power 
of  the  stomach  and  the  intestines  to  digest  and  absorb  proteid  food.  Further 
details  upon  this  point  will  be  given  presently,  in  describing  the  nutritive 
value  of  the  food-stuffs. 

Carbon  Equilibrium. — The  term  "  carbon  equilibrium  "  is  sometimes  used 
to  describe  the  condition  in  which  the  total  carbon  of  the  excreta  (occurring  in 
the  C02,  urea,  etc.)  is  exactly  covered  by  the  carbon  of  the  food.  As  one  can 
readily  understand,  an  animal  might  be  in  a  condition  of  nitrogen  equilibrium 
and  yet  be  losing  or  be  gaining  in  weight,  since,  although  the  consumption  of 
proteids  in  the  body  might  just  be  covered  by  the  proteids  of  the  food,  the 
consumption  of  non-proteids,  fats  and  glycogen,  might  be  greater  or  less  than 
was  covered  by  the  supply  of  food.  In  addition,  we  might  speak  of  mi  equi- 
librium as  regards  the  water,  salts,  etc.,  although  these  terms  are  not  generally 
used.  An  adult  in  good  health  usually  so  lives  as  to  keep  in  both  nitrogen 
and  general  body  equilibrium — that  is,  to  maintain  his  normal  weight — while 
slight  variations  in  weight  from  time  to  time  are  probably  for  the  most  part 
due  to  a  loss  or  a  gain  in  body-fat — in  other  words,  to  changes  in  the  carbon 
equilibrium. 

Nutritive  Importance  of  the  Proteids. — The  digestion  and  absorp- 
tion of  proteids  have  been  considered  in  previous  sections.  We  believe  that 
the  digested  proteid,  with  the  exception  of  the  variable  quantity  that  suffers 
decomposition  in  the  intestine  as  a  result  of  putrefaction  or  of  the  prolonged 
action  of  trypsin,  is  absorbed  into  the  blood  after  undergoing  an  unknown 
modification  during  the  act  of  absorption.  Subsequently  tins  proteid 
materia]  passes  into  the  lymph  ami  is  broughl  into  contacl  with  the 
tissues.  lt>  main  nutritive  importance  lies  in  its  relations  to  the  tissues, 
and,  speaking  generally,  we  may  say  that  the  final  late  of  the  proteid 
molecule  is  that  it  undergoes  a  physiological  oxidation  whereby  the  complex 
molecule  is  broken  down  to  form  the  simpler  and  more  stable  compounds, 
C02,  H20,  urea,  sulphates  and  phosphates.  This  destruction  of  the  proteid 
molecule  takes  place  in  or  under  the  influence  of  the  living  cells,  and  it 
gives  rise  to  a  liberation  of  energy  mainly  in  the  form  of  heat.  It  is 
impossible  to  follow  the  various  ways  in  which  this  physiological  oxidation 
takes  place.  It  is  probable,  however,  that  some  of  the  proteid  undergoes 
destruction  without  becoming  a  part,  an  organized  part,  of  the  living  cells, 
although  its  oxidation  is  effected  through  the  agency  of  the  cells.  It  has  been 
proposed  by  Yoit  '  to  designate  the  proteid  that  is  oxidized  in  this  way  as 
1  Hermann's  Handbuch  der  Physiobgie,  1881,  Bd.  vi.  S.  300. 


346  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

"the  circulating  albumin  or  proteid."  According  to  Voit,  a  well-fed  animal 
has  in  its  lymph  and  tissues  always  a  certain  excess  of  proteid  which  is  to 
undergo  the  fate  of  the  circulating  proteid,  and  this  supposition  is  used  to 
explain  the  fact  that  for  the  first  day  or  so  a  starving  animal  metabolizes 
more  proteid,  as  determined  by  the  nitrogenous  excreta,  than  in  the  subse- 
quent days,  after  the  supply  of  the  circulating  proteid  has  been  destroyed. 
A  portion  of  the  proteid  food,  however,  before  its  final  destruction  is  utilized 
to  replace  the  nitrogenous  waste  of  the  tissues  ;  it  is  built  up  into  living  proto- 
plasm to  supply  the  place  of  organized  tissue  that  has  undergone  disassimi- 
lation  or  to  furnish  new  tissue  in  growing  animals.  To  the  proteid  that  is 
built  up  into  tissue  Voit  gives  the  name  of  "  organeiweiss,"  the  best  translation 
of  which,  perhaps,  is  "  tissue-proteid."  It  should  be  stated  that  this  division 
of  the  proteid  into  circulating  proteid  and  tissue-proteid  has  been  severely 
criticised  by  some  physiologists,  but  it  has  the  merit  at  least  of  furnishing. 
a  simple  explanation  of  some  curious  facts  with  regard  to  the  use  of  proteid 
in  the  body.  To  avoid  misunderstanding,  it  is  well  to  say  that  the  sepa- 
ration into  circulating  proteids  and  tissue-proteids  does  not  mean  that  the 
proteid  that  is  absorbed  from  the  alimentary  canal  is  of  two  varieties. 
The  terms  refer  to  the  final  fate  of  the  proteid  in  the  body:  a  certain 
portion  is  utilized  to  replace  protoplasmic  tissue,  and  it  then  becomes  "  tis- 
sue-proteid," while  the  balance  is  metabolized  in  various  ways  and  con- 
stitutes the  "circulating  proteid."  Any  given  molecule  of  proteid,  as  far 
as  is  known,  may  fulfil  either  function.  With  regard  to  the  general  nutri- 
tive value  of  piot eids,  it  has  been  demonstrated  clearly  that  they  are  abso- 
lutely necessary  for  the  formation  of  protoplasmic  tissue.  An  animal  fed  only 
on  non-nitrogenous  food  such  as  fats  and  carbohydrates  will  inevitably  starve 
to  death  in  time  :  this  has  been  shown  by  actual  experiments,  and,  besides,  it 
follows  from  a  priori  considerations.  Protoplasm  contains  nitrogen;  fats  and 
carbohydrates  are  non-nitrogenous,  and  therefore  cannot  be  used  to  make  new 
protoplasmic  material.  It  is  requisite,  moreover,  not  only  that  the  food  shall 
contain  some  nitrogen,  but  that  this  nitrogen  shall  be  in  the  form  of  proteid. 
If  an  animal  is  fed  upon  a  diet  containing  fats  and  carbohydrates  and  nitrog- 
enous material  other  than  proteids,  such  as  amido-acids  or  gelatin,  nitrogenous 
equilibrium  cannot  be  maintained.  There  will  be  a  steady  loss  of  nitrogen  in 
the  excreta,  due  to  a  breaking-down  of  proteid  tissue  within  the  body,  and  the 
final  result  of  maintaining  such  a  diet  would  be  the  death  of  the  animal.  It 
may  be  said,  then,  with  regard  to  animal  metabolism  that  proteid  food  is 
absolutely  necessary  for  the  formation  of  new  protoplasm;  its  place  in  this 
respect  cannol  betaken  by  any  other  element  of  our  food.  lint,  in  addition  to 
this  use.  proteid,  as  has  been  described  above,  may  be  oxidized  in  the  body  with- 
out being  first  constructed  into  protoplasmic  material.  According  to  an  older 
theory  in  physiology,  advanced  by  Liebig,  food-stuffs  were  either  plastic  or 
respiratory;  by  plastic  foods  he  meant  those  that  are  built  into  tissue,  and  he 
supposed  that  the  proteid-  belonged  to  this  class ;  by  respiratory  foods  he  meant 
those  that  are  oxidized  or  burnt  in  the  body  to  produce   heat  :   the   fats  and 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  347 

carbohydrates  constituted  this  class.  We  now  know  that  proteids  are  respi- 
ratory as  well  as  plastic  in  the  terms  of  this  theory ;  they  serve  as  sources  of 
energy  as  well  as  to  replace  tissue,  and  Liebig's  classification  has  therefore 
fallen  into  disuse.  Our  present  ideas  of  the  twofold  use  of  proteid  food  may 
be  supported  by  many  observations  and  experiments,  but  perhaps  the  most 
striking  proof  of  the  correctness  of  these  views  is  found  in  the  fact  that  a  car- 
nivorous animal  can  be  kept  in  both  nitrogen  and  carbon  equilibrium  upon  a 
meat  diet  only,  excluding  for  the  time  a  consideration  of  the  water  and  inorganic 
salts.  Pettenkofer  and  Voit  kept  a  dog  weighing  30  kilograms  in  nitrogen 
and  carbon  equilibrium  upon  a  diet  of  1500  grams  of  lean  meat  per  day,  and 
by  increasing  the  diet  to  2500  grams  per  day  the  animal  even  gained  in  weight, 
owing  to  an  increase  in  fat.  Pfliiger  states  also  that  he  was  able  to  keep  a  dog 
in  body-equilibrium  as  long  as  eight  months  upon  a  meat  diet.  Facts  like 
these  demonstrate  that  the  animal  organism  may  get  all  its  necessary  energy 
from  proteid  food  alone,  although,  as  we  shall  see  later,  it  is  more  econom- 
ical and  more  beneficial  to  get  a  part  of  it  at  least  from  the  oxidation  of 
fats  and  carbohydrates.  Adopting  the  theory  of  "  circulating  proteids,"  we 
may  say  that  any  excess  of  proteid  above  that  utilized  for  tissue-repair 
or  tissue-growth  will  be  metabolized  in  the  body,  with  the  liberation  of 
energy.  It  makes  no  difference  how  much  proteid  material  we  consume : 
the  excess  beyond  that  used  to  replace  tissue  is  quickly  destroyed  in  some 
way,  and  its  nitrogen  appears  in  the  urine  as  urea  or  one  of  the  related 
compounds.  A  good  example  of  the  power  of  the  tissues  to  oxidize  large 
amounts  of  proteid  is  given  in  the  following  experiment,  selected  from  a 
paper  by  Pfliiger.  Dog,  weight  28.1  kilograms,  fed  at  11a.  m.  with  2070.7 
grams  of  meat : 

2070.7  grams  of  meat  contain G9.2  grams  X. 

Total  nitrogen  eliminated  in  urine  and  feces  in  twenty-four 

hours  (7  a.m.  to  7  a.m.) 71.2      "        " 

Deficit  of  N 0.96  grams. 

The  total  nitrogen  in  the  urine  alone  was  68.5  grams. 

In  urine  from  7  a.m.  to  1 1  a.  m.,  the  fasting  period 6.9  grams. 

In  urine  from  11  a.m.  to  7  a.  m.,  time  after  feeding 61.6      " 

Therefore  in  the  four  hours  of  fasting  the  animal  eliminated  in  his  urine 
1.7  grams  N  per  hour,  while  in  the  twenty  hours  after  eating  he  excreted 
3.1  grams  N  per  hour.  This  experiment  shows  not  only  the  completeness 
with  which  an  excessive  proteid  diet  is  handled  by  the  tissues,  but  also  the 
rapidity  with  which  the  excess  is  destroyed.  In  so  far  as  proteid  food  is  burnt 
in  the  body  only  as  a  source  of  energy  and  without  being  used  to  form  new  tis- 
sue, its  place  can  be  supplied  in  part,  but  only  in  part,  by  non-nitrogenous  food- 
stuffs— carbohydrates  and  fats.  The  double  use  of  proteid  as  a  tissue-former  and 
an  energy-producer  would  seem  to  imply  that  if,  in  any  given  case,  sufficient  pro- 
teid were  used  in  the  diet  to  cover  the  tissue-waste,  the  balance  of  the  diet  might 
Decomposed  of  fats  and  carbohydrates,  and  the  animal  thereby  be  kepi  in  aitrog- 


348  AN   AMERICAN    TEXT-HOOK   OF   PHYSIOLOGY. 

enous equilibrium.  Apparently  this  is  not  the  case,  as  is  seen  from  experiments 
of  the  following  character  :  When  an  animal  is  allowed  to  starve,  the  nitrogen  in 
the  urine,  after  the  first  few  days,  becomes  practically  constant,  and  represents 
the  amount  of  oxidation  of  proteid  tissue  taking  place  in  the  body.  If,  now,  the 
animal  is  given  an  amount  of  proteid  just  equal  to  that  being  destroyed  in  the 
body,  nitrogenous  equilibrium  is  not  established;  some  of  the  body-proteid  con- 
tinues to  be  lost,  and  to  get  the  animal  into  equilibrium  a  comparatively  large 
exee—  of  proteid  must  be  given  in  the  food.  The  same  result  holds  if  carbo- 
hydrate- and  fats  are  given  along  with  the  proteid,  with  the  exception  that  upon 
this  diet  nitrogen  equilibrium  is  more  readily  established — that  is,  less  proteid 
is  required  in  the  food.  Upon  the  theory  of  circulating  proteids  and  tissue- 
proteids,  this  fact  may  lie  accounted  for  by  saying  that  of  the  proteid  given  as 
food,  a  part  always  undergoes  destruction  as  circulating  proteid  without  going 
to  form  tissue,  so  that  to  cover  tissue-waste  a  larger  amount  of  proteid  must  be 
taken  a-  food  than  would  be  necessary  if  it  could  all  be  used  exclusively  for  the 
repair  of  tissue.  Carbohydrates  and  fats  diminish  the  amount  of  proteid 
destroyed  as  circulating  proteid,  and  thereby  enable  us  to  keep  in  nitrogen 
equilibrium  on  a  smaller  proteid  diet.  With  albuminoid  food  (gelatin)  the 
facts  seem  to  be  different.  If  albuminoids  be  given  in  the  food  together  with 
proteids  or  with  proteids  and  a  non-nitrogenous  food-stuff  (fats  or  carbo- 
hydrates), nitrogen  equilibrium  may  be  established  upon  a  much  smaller 
amount  of  proteid  thau  in  the  case  of  a  diet  consisting  of  proteid  alone  or  of 
proteid  together  with  fats  and  carbohydrates.  It  seems  probable  that  albu- 
minoids can  take  the  place  entirely  of  circulating  proteids,  so  that  only  enough 
proteid  need  be  given  to  cover  actual  tissue-waste.  This  point  will  be  referred 
to  again  in  speaking  of  the  value  of  the  albuminoids. 

Z/UXU8  <  bnmmption. — The  fact  that  normally  more  proteid  is  eaten,  even 
in  a  mixed  diet,  than  is  necessary  to  cover  the  actual  tissue-waste  led  some  of 
the  older  physiologists  to  speak  of  the  excess  as  unnecessary,  a  luxus,  and  the 
rapid  destruction  of  the  excess  in  the  body  was  described  as  a  "  luxus  con- 
sumption." There  can  be  no  doubt  about  the  fact  that  proteid  may  be,  and 
normally  is,  eaten  in  excess  of  what  is  necessary  to  repair  tissue-waste,  or  in 
excess  of  what  is  requisite  to  maintain  nitrogenous  equilibrium  at  a  low 
level.  But  it  is  altogether  improbable  that  the  excess  is  really  a  "luxus." 
It  has  been  stated,  in  speaking  of  nitrogenous  equilibrium,  that  an  animal 
may  be  kept  in  this  condition  upon  a  certain  minimal  amount  of  pro- 
teid, or  upon  various  larger  amounts  up  to  the  limit  of  the  power  of  the 
alimentary  canal  to  digest  and  absorb;  but  it  has  also  been  shown  (Munk1) 
that  if  an  animal  i<  i^(\  upon  a  diet  containing  quantities  of  proteid  barely 
sufficient  to  maintain  N  equilibrium,  it  will  after  a  time  show  signs  of  mal- 
nutrition. It  seems  to  be  necessary,  as  Pfliiger  pointed  out,  that  the  tissues 
should  have  a  certain  excess  of  proteid  t<>  destroy  in  order  that  their  nutri- 
tional or  metabolic  powers  may  be  kept  in  a  condition  of  normal  activity. 
Hence  we  find  that  well-nourished  individuals  habitually  consume  more  proteid 
than  would  theoretically  suffice  for  N  equilibrium.  For  example,  the  average 
1  I>n  Bois-Reymond's  Arehivjur  Physiologie,  1891,  S.  338. 


CHEMISTRY  OF  DIGESTION  AND  NUTRITION.  349 

diet  of  an  adult  male  contains,  or  should  contain,  from  100  to  118  grams  of 
proteid  per  day,  but  it  has  been  shown  that  nitrogen  and  body  equilibrium  in 
man  may  be  maintained,  for  short  periods  at  least,  upon  40  or  even  20'  grama 
of  proteid  a  day,  provided  large  amounts  of  i'ats  or  carbohydrates  are  eaten. 
It  is  scarcely  necessary  to  add  that  this  beneficial  excess  has  a  limit,  and  that 
too  great  an  excess  of  proteid  food  may  cause  troubles  of  digestion  as  well  as 
of  general  nutrition. 

Nutritive  Value  of  Albuminoids. — The  albuminoid  most  frequently  oc- 
curring in  food  is  gelatin.  It  is  derived  from  collagen  of  the  connective 
tissues.  Collagen  of  bones  or  of  connective  tissue  takes  up  water  when  boiled 
and  becomes  converted  into  gelatin.  We  eat  gelatin,  therefore,  in  boiled  meats, 
soups,  etc.,  and,  besides,  it  is  frequently  employed  directly  as  a  food  in  the 
form  of  table-gelatin.  Collagen  has  the  following  percentage  composition  : 
C,  50.75  per  cent;  H,  6.47  ;  N,  17.86;  O,  24.32;  S,  0.6.  It  resembles  the 
proteid  molecule  closely  in  percentage  composition,  and  it  would  seem  that  the 
tissues  might  use  it  as  they  do  proteid,  for  the  formation  of  new  protoplasm. 
Experiments,  however,  have  demonstrated  clearly  that  this  is  not  the  case. 
Animals  fed  upon  albuminoids  together  with  fats  and  carbohydrates  do  not 
maintain  N  equilibrium;  a  certain  proportion  of  tissue  breaks  down,  giving 
an  excess  of  nitrogen  in  the  urine.  The  final  result  of  such  a  diet  would  be 
continued  loss  of  weight  and,  finally,  malnutrition  and  death.  Gelatin,  how- 
ever, is  readily  digested,  gelatoses  and  gelatin  peptones  being  formed  ;  these 
are  absorbed  and  oxidized  in  the  body,  with  the  formation  of  C02,  H20,  and 
urea  or  some  related  nitrogenous  product.  Gelatin  serves,  then,  as  a  source 
of  energy  to  the  body  in  the  same  sense  as  do  carbohydrates  and  fats.  When 
any  one  of  these  three  substances  is  used  in  a  diet,  the  proportion  of  proteid 
necessary  for  the  maintenance  of  X  equilibrium  may  be  reduced  greatly.  I  Fpon 
the  theory  of  circulating  proteids,  this  is  explained  by  saying  that  these  sub- 
stances are  burnt  in  place  of  proteid,  and  that  the  proportion  of  this  latter 
material  which  undergoes  the  fate  of  circulating  proteid  is  thereby  diminished. 
Actual  experiments  have  shown  that  gelatin  is  more  efficacious  than  either  Hits 
or  carbohydrates  in  protecting  the  proteid  in  the  body,  and  it  has  been  sug- 
gested, therefore,  that  it  may  take  the  place,  partly  or  completely,  of  the  circu- 
lating proteid,  according  to  the  amount  icd.  If  this  suggestion  is  true,  we 
may  say  that  gelatin  has  a  nutritive  value  the  same  as  that  of  the  proteids, 
except  that  it  cannot  be  constructed  into  living  proteid.  The  relative  value 
of  fats,  carbohydrates,  and  gelatin  in  protecting  proteid  from  destruction  in 
the  body  is  illustrated  by  the  following  experiment,  reported  by  Voit.  A  dog- 
weighing  .32  kilograms  was  led  alternately  upon  proteid  ami  sugar,  proteid 
and  fat,  and  proteid  and  gelatin  : 


Nourishment 

(gi 

r:unsi. 

Calcn 

ilated  destruction 

of  flesh 

Meat. 

Gelal  in. 

Kat. 

Sugar. 

in  body  (grams). 

4l«) 

— 

200 

— 

150 

400 

— 

— 

250 

439 

400 

200 

— 

— 

356 

■Sivt'n:  Skandinavischu  Arehiv  fur  Physiologic    1899,  Bd.  10,  S.  91. 


350  AN  AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

Practically,  however,  the  use  of  gelatin  in  diets  is  restricted  by  its  unpalata- 
bleness  when  used  in  large  quantities.  Whatever  may  be  the  physiological  cause 
of  this  peculiarity,  there  seems  to  be  no  doubt  that  when  employed  largely  in  the 
diet  both  animals  and  men  soon  develop  such  an  aversion  to  it  that  it  is  necessary 
to  discontinue  its  use.  Munk  '  has  attempted  to  determine  how  tar  the  proteids 
offood  maybe  replaced  by  gelatin.  In  these  experiments  a  dog  was  brought  into 
a  condition  of  nitrogenous  equilibrium  upon  a  diet  of  flesh,  meal,  rice,  and  lard, 
containing  9.73  grams  of  nitrogen.  During  the  period  this  diet  was  continued  the 
animal,  whose  weight  was  16.5  kilograms,  was  oxidizing  in  its  body  3.7  grams 
ofproteid  daily  for  each  kilogram  of  weight.  In  a  second  period  lasting  four 
davs  the  quantities  of  rice  and  lard  were  the  same  as  before,  but  the  proteid  in 
its  diet  was  reduced  to  8.2  grams,  which  contained  1.3  grams  of  nitrogen  ;  the 
balance  of  the  necessary  nitrogen  was  supplied  in  the  form  of  gelatin,  so  that  in 
round  numbers  only  one-seventh  of  the  required  daily  amount  of  nitrogen  was 
given  as  proteid.  rFhc  result  was  that  the  animal  maintained  its  nitrogen  equi- 
librium for  the  short  period  stated.  It  was  found  that  the  experiments  could 
not  be  continued  longer  than  four  days,  owing  to  the  growing  dislike  of  the 
animal  for  the  gelatin  food.  During  the  second  period  the  animal  was  receiving 
in  its  food  and  burning  in  its  body  only  0.5  gram  of  proteid  daily  for  each 
kilogram  of  weight,  as  against  3.7  grams  upon  a  normal  diet.  It  is  usually 
stated  that  it  is  not  possible  to  substitute  fats  or  carbohydrates  for  the  proteids 
of  our  diet  to  the  same  extent,  but  the  experiments  of  Siven  quoted  on  the 
preceding  page  indicate  that  this  common  belief  may  be  incorrect. 

Nutritive  Value  of  Fats. — The  fats  of  food  are  absorbed  into  the  lacteals 
as  neutral  fats.  They  eventually  reach  the  blood  in  this  condition,  and  are 
afterward  in  some  way  consumed  by  the  tissues.  The  final  products  of  their 
oxidation  must  be  the  same  as  when  burnt  outside  the  body — namely,  0O2 
and  H20 — and  a  corresponding  amount  of  energy  must  be  liberated.  Speak- 
ing generallv,  then,  the  essential  nutritive  value  of  the  fats  is  that  they  furnish 
energv  to  the  body,  and,  from  a  chemical  standpoint,  they  must  contain  more 
available  energy,  weight  for  weight,  than  the  proteids  or  the  carbohydrates 
(see  p.  365).  In  a  well-nourished  animal  a  large  amount  of  fat  is  found 
normally  in  the  adipose  tissues,  particularly  in  the  so-called  "panniculus 
adiposus"  beneath  the  skin.  Physiologically,  this  body-fat  is  to  be  regarded 
a-  a  reserve  supply  of  nourishment.  When  food  is  eaten  and  absorbed  in 
excess  of  the  actual  metabolic  processes  of  the  body,  the  excess  is  stored  in 
the  adipose  tissue  as  fat,  to  be  drawn  upon  in  case  of  need — as,  for  instance, 
during  partial  or  complete  starvation.  A  starving  animal,  after  its  small 
supply  of  glycogen  is  exhausted,  lives  entirely  upon  body-proteids  and  fats; 
the  larger  the  supply  of  fat,  the  more  effectively  will  the  proteid  tissues  be 
protected  from  desi  met  ion.  In  accordance  with  this  fact,  it  has  been  shown 
that  when  subjected  to  complete  starvation  a  fat  animal  will  survive  longer 
than  a  lean  one.  Our  supply  of  fat  is  called  upon  not  only  during  complete 
abstention  from  food,  but  also  whenever  the  diet  is  insufficient  to  cover  the 
oxidations  of  the  body,  as  in  deficient  food,  sickness,  etc. 

1  Pjlugcr's  Arrhii  fur  'He  gesammte  Phyniologie,  1894,  Bde.  lviii.  S.  309. 


CHE3IISTBY  OF  DIGESTION  AND   NUTRITION.  35] 

Formation  of  Pat  in  the  Body. — The  origin  of  body-fat  has  always  been 
an  interesting  problem  to  physiologists.  Naturally,  the  first  supposition  made 
was  that  it  comes  directly  from  the  fat  of  the  food.  According  to  this  view, 
a  certain  proportion  of  the  fat  of  the  food  was  supposed  to  be  deposited  directly 
in  the  cells  of  adipose  tissue,  and  in  this  way  all  our  supply  of  fat  originated. 
This  theory  was  soon  disproved.  It  was  shown,  especially  upon  cows  and  pigs, 
that  the  amount  of  fat  formed  in  the  body  within  a  given  time,  including  the 
fat  of  milk  in  the  case  of  the  cow,  might  be  far  in  excess  of  the  total  amount 
of  fat  taken  in  the  food  during  the  same  period,  thus  demonstrating  that  a  cer- 
tain proportion  at  least  of  the  body-fat  must  have  some  other  origin.  More- 
over, the  genesis  of  the  fat-droplets  in  fat-cells,  as  studied  under  the  microscope, 
did  not  agree  with  the  old  view  ;  and  there  was  the  further  fact  that  each  animal 
has  its  own  peculiar  kind  of  fat;  as  Liebig  says,  "In  hay  or  the  other  fodder 
of  oxen  no  beef-suet  exists,  and  no  hog's  lard  can  be  found  in  the  potato  refuse 
given  to  swine."  In  fact,  the  evidence  was  so  conclusive  against  this  theory  that 
physiologists  for  a  time  were  led  to  adopt  the  opposite  view  that  no  fat  at  all  can 
be  obtained  directly  from  the  fat  of  the  food.  However,  it  has  now  been  shown 
that  under  certain  conditions  fat  may  be  deposited  directly  in  the  tissues  from 
the  fat  of  food.  Lebedeff,  and  afterward  Munk,  proved  that  if  a  dog  is  first 
starved  until  the  reserve  supply  of  fat  in  the  body  is  practically  used  up,  and 
it  is  then  fed  richly  upon  foreign  fats,  such  as  rape-seed  oil,  linseed  oil,  or 
mutton  tallow,  it  will  again  lay  on  fat,  and  some  of  the  foreign  fat  may  he 
detected  in  its  body.  The  conditions  necessary  to  be  fulfilled  in  order  to  get 
this  result  make  it  probable  that  under  normal  conditions  none  of  the  fat  of 
the  body  is  derived  directly  from  the  fat  of  the  food.  On  the  contrary,  the 
fat  of  the  food  is  completely  oxidized,  and  our  body-fat  is  normally  o in- 
structed anew  from  either  proteids  or  carbohydrates.  As  to  its  origin  from 
proteid,  Voit  has  devoted  numerous  researches  to  the  purpose  of  demon- 
strating that  this  is  the  main  source  of  body-fat.  His  belief  is  that  in  the 
course  of  metabolism  the  proteid  molecule  undergoes  a  cleavage,  with  the  for- 
mation of  a  nitrogenous  and  a  non-nitrogenous  part.  The  former,  after  further 
changes,  is  eliminated  in  the  form  of  urea,  etc. ;  the  latter  may  be  converted 
into  fat,  or  possibly  into  glycogen.  The  theoretical  maximum  of  fat  which 
can  arise  in  this  way  is  51.5  per  cent,  of  the  entire  amount  of  proteid.  Voit 
attempted  to  demonstrate  this  theory  by  actual  experiments.  lb'  showed  that 
dogs  fed  upon  large  amounts  of  lean  meat  did  not  give  off  as  much  carbon  in 
the  excreta  as  they  received  in  the  food.  The  excess  of  carbon  must  have  been 
retained  in  the  body,  and,  in  all  probability,  in  the  form  of  fat.  As  corrob- 
orative evidence  he  cites  the  apparently  direct  conversion  of  proteid  material 
into  fat  in  such  cases  as  the  formation  of  lat-droplets  in  the  fat-cells  or  cells 
of  the  mammary  glands,  and  in  muscle-fibres  and  liver-cells  undergoing  fatty 
degeneration  ;  but  evidence  of  this  latter  character  is  not  conclusive,  since  we 
have  no  immediate  proof  that  the  faf  arises  directly  from  the  proteid  material 
in  the  cells.  Voit's  experimental  evidence  has  been  questioned  recently  by 
Pfliiger,  his  criticisms  being  directed  mainly  toward   the  calculations   involved 


3,52  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

in  Vbit's  experiments.  The  result  of  this  criticism  has  been  to  make  us  more 
cautious  in  attributing  the  origin  of  body-fat  solely  or  mainly  to  proteids,  hut 
as  regards  the  possibility  of  some  proteid  being  converted  into  fat  in  the  body 

there  can  be  do  reasonable  doubt.  It  has  been  proved  (p.  328)  that  glycogen 
may  be  formed  from  proteid,  and  since  it  is  now  generally  accepted  that  fats 
are  formed  from  carbohydrates,  the  possibility  of  an  indirect  production  of  fats 
from  proteid-  seems  to  follow  necessarily. 

The  connection  between  the  carbohydrates  of  the  food  and  the  fat  of  the 
body  has  been  a  subject  of  discussion  and  investigation  anions:  physiologists 
for  a  number  of  years.  It  was  the  original  belief  of  Liebig  that  carbohydrates 
are  the  source  of  body-fat.  This  view  was  afterward  abandoned  under  the 
influence  of  the  work  of  Pettenkofer  and  Voit,  but  renewed  investigations  seem 
to  have  re-established  it  upon  -olid  experimental  grounds.  In  some  older 
experiments  of  Lawes  and  Gilbert  it  was  shown  that  the  fat  laid  on  by  a  young 
pig  during  a  certain  period  was  greater  than  could  be  accounted  for  by  the 
total  fat  in  the  food  during  that  period,  plus  the  theoretical  maximum  obtain- 
able from  the  proteid  fed  during  the  same  time.  Of  more  recent  experiments 
demonstrating  the  same  point,  a  single  example  may  be  quoted  from  Rubiier.1 
a-  follow-:  A  small  dog,  weighing  6.2  kilograms,  was  fed  richly  with  meat  for 
two  davs  and  was  then  starved  for  two  days  ;  its  weight  at  the  end  of  this  time 
was  5.89  kilograms.  The  animal  was  then  given  for  two  days  a  diet  of  cane- 
sugar  100  grams,  starch  85  grams,  and  fat  4.7  grams.  It  was  kept  in  a  respira- 
tion apparatus  and  its  total  excretion  of  nitrogen  and  carbon  was  determined : 

Total  C  excretion 87.10  grams  C. 

"       C  ingesta 176.fi        "       " 

89.5         "       "     retained  in  the  body. 

flu-  total  nitrogen  excreted  =  2.55  grams.  The  carbon  contained  in  the  pro- 
teid thus  broken  down  plus  that  in  the  4.7  grams  of  fat  =  13  grams.  If  we 
make  the  assumption  that  all  of  the  C  from  these  two  sources  was  retained 
within  the  body,  there  would  still  be  a  balance  of  76.5  grams  C  (89.5 —  13.0) 
which  must  have  been  stored  in  the  body  either  as  glycogen  or  as  fat.  The 
greatest  possible  storage  of  glycogen  was  estimated  at  78  grams  =  34.6  grams 
C,  so  that  76.5  —  34.6  =  41.9  grams  C  as  the  minimal  amount  which  must 
have  been  retained  as  fat  and  must  have  arisen  from  the  carbohydrates  of  the 
food.  Similar  experiments  have  been  made  upon  herbivorous  animals,  and 
as  the  result  of  investigations  of  this  character  we  are  compelled  to  admit  that 
the  carbohydrates  form  one  source,  and  possibly  the  main  source,  from  which 
the  body-fats  arc  derived.  This  belief  accords  with  the  well-known  fact  that 
in  fattening  stock  the  best  diet  is  one  containing  a  large  amount  of  carbo- 
hydrate  together  with  a  certain  quantity  of  proteid.  On  the  view  that  fats 
were  formed  only  from  proteids,  the  efficacy  of  the  carbohydrates  in  such  a  diet 
was  supposed  to  lie  in  the  fact  that  they  protected  a  part  of  the  proteid  from 
oxidation,  and  thus  permitted  the  formation  offal  from  proteid;  but  it  is  now 
believed  that  the  carbohydrates  of  a  fattening  diet  are,  in  part,  converted 
1  Zeitschrift  fiir  Biologie,  1SS6,  Bd.  22,  8.  272. 


CHEMISTRY  OF  DIGESTION  AND   N  (TUITION.  353 

directly  to  fat,  although  the  chemistry  of  the  transformation  is  not  as  yet 
understood.  Diets,  such  as  the  well-known  Banting  diet,  intended  to  reduce 
obesity  are  characterized,  on  the  contrary,  by  a  small  proportion  of  carbo- 
hydrates and  a  relative  excess  of  proteid. 

Nutritive  Value  of  Carbohydrates. — The  nutritive  importance  of  the 
carbohydrates  is  similar  in  general  to  that  of  the  fats ;  they  are  oxidized  aud 
furnish  energy  to  the  body.  In  addition,  as  has  been  described  in  the  pre- 
ceding paragraph,  they  may  be  converted  into  fat  and  stored  in  the  body  as 
a  reserve  supply  of  nourishment.  As  a  matter  of  fact,  the  carbohydrates  form 
the  bulk  of  ordinary  diets.  They  are  easily  digested,  easily  oxidized  in  the 
body,  and  from  a  financial  standpoint  they  form  the  cheapest  food-stuff.  The 
final  products  in  the  physiological  oxidation  of  carbohydrates  must  be  CO,  and 
H20.  Inasmuch  as  the  H  and  O  in  the  molecule  already  exist  in  the  proper 
proportions  to  form  H20  (C6HI206,  C12H22On),  it  follows  that  relatively  less  oxy- 
gen will  be  needed  in  the  combustion  of  carbohydrates  than  in  the  case  of  proteids 
or  of  fats.  Whatever  may  be  the  actual  process  of  oxidation,  we  may  consider  that 
only  as  much  O  is  needed  as  will  suffice  to  oxidize  the  C  of  the  sugar  to  COa. 

CO 

Hence  the  ratio  of  O  absorbed  to  CO.,  eliminated,  -=-^,  a  ratio  that  is  known 

o2 

as  the  respiratory  quotient,  will  approach  nearer  to  unity  as  the  quantity  of 
carbohydrates  in  the  diet  is  increased.  From  our  study  of  the  digestion  of 
carbohydrates  (p.  318)  we  have  found  that  most  of  the  carbohydrates  of  our 
food  pass  into  the  blood  as  dextrose  (or  levulose),  and  any  excess  above  a  cer- 
tain percentage  is  converted  temporarily  to  glycogen  in  the  liver,  the  muscles, 
etc.,  to  be  again  changed  to  dextrose  before  being  used.  The  sugar  undergoes 
final  oxidation  in  the  tissues  to  CO,  and  H20.  While  it  is  possible  that  this 
oxidation  may  be  direct — that  is,  that  the  sugar  may  be  burnt  directly  to  COa  and 
H20 — it  is  usually  supposed  to  be  preceded  by  a  splitting  of  the  sugar  mole- 
cule, although  the  steps  in  the  process  are  not  definitely  known. 

There  has  been  discovered  recently  in  connection  with  the  pancreas  a  num- 
ber of  facts  that  are  interesting  not  only  in  themselves,  but  doubly  so  because 
they  promise,  when  more  fully  investigated, to  throw  some  light  on  the  man- 
ner of  consumption  of  sugar  by  the  tissues.  (See  also  section  on  Internal 
Secretions.)  It  has  been  shown  by  yon  Mering  and  Minkowski  '  and  others 
that  if  the  pancreas  of  a  dog  is  completely  removed,  the  tissues  lose  the  power 
of  consuming  sugar,  so  that  it  accumulates  in  the  blood  and  finally  escapes  in 
the  urine,  causing  what  has  been  called  "pancreatic  diabetes."  If  a  small 
part  of  the  pancreas  is  left  in  the  body, even  though  it  is  not  connected  by  its 
duct  with  the  duodenum,  diabetes  does  not  occur.  The  inference  usually  made 
from  these  experiments  is  that  the  pancreas  gives  off  something  to  the  blood — an 
internal  secretion — that  is  necessary  to  the  physiological  consumption  of  sugar. 
In  what  way  the  pancreas  exerts  this  influence  has  vet  to  be  discovered  ; 
possibly  it  is  through  the  action  of  a  specific  enzyme  that  helps  to  break 
down    the   sugar;   possibly  it  is  by  some   other   means.       Bui  the  necessity  of 

1  Arrliir/iir  experimentelle  Pathologic  uml  Pharmakologie,  1893,  xxxi.  S.  85. 
Vol.  I.— 23 


354  AN  AMERICAN    TEXT-BOOK   OE  PHYSIOLOGY. 

the  pancreas  in  some  way  for  the  normal  consumption  of  sugar  by  the  tissues 
generally  seems  to  be  indisputably  established.  It  is  a  discovery  of  the  utmost 
importance  in  its  relations  to  the  normal  nutrition  of  the  body,  and  also 
because  of  its  possible  bearing  on  the  pathological  condition  known  as  diabetes 
mellitus.  In  this  latter  disease  the  tissues,  for  some  reason,  are  unable  to 
oxidize  the  sugar  in  normal  amounts,  and  a  good  part  of  it,  therefore,  escapes 
through  the  urine.  The  facts  and  theories  bearing  upon  diabetes  are  of 
unusual  interest  in  connection  with  the  nutritive  history  of  the  carbohydrates, 
but  for  a  fuller  description  reference  must  be  made  to  more  elaborate  works. 

Another  statement  in  connection  with  the  fate  of  sugar  in  the  body  is 
worthy  of  a  brief  reference:  It  has  been  asserted  by  Lepine  and  Barral  that 
there  is  normally  present  in  blood  an  enzyme  capable  of  destroying  sugar. 
Their  theory  rests  upon  the  undoubted  fact  that  sugar  added  to  blood  outside 
the  body  soon  disappears.  They  call  the  process  "  glycolysis,"  and  the  enzyme 
to  which  they  attribute  this  disappearance  the  "glycolytic  enzyme."  Others, 
however  (Arthus),  have  claimed  that  this  enzyme  is  only  a  post-mortem  result 
of  the  disintegration  of  the  corpuscles  of  the  blood,  and  that  it  is  not  present 
in  circulating  blood.  We  must  await  further  investigation  upon  this  point, 
and  be  content  here  with  a  mere  reference  to  the  subject. 

Nutritive  Value  of  "Water  and  Salts. — Water  is  lost  daily  from  the  body 
in  large  quantities  through  the  kidney,  the  skin,  the  lungs,  and  the  feces,  and 
it  is  replaced  by  water  taken  in  the  food  or  separately,  and  partially  also  by 
the  water  formed  in  the  oxidations  of  the  body.  A  certain  percentage  of 
water  in  the  tissues  and  in  the  liquids  of  the  body  is  naturally  absolutely 
essential  to  the  normal  play  of  metabolism  ;  and  conditions,  such  as  muscular 
exercise,  that  increase  the  water-loss  bring  about  also  an  increased  water- 
consumption,  the  regulation  being  effected  through  the  nervous  mechanism 
that  mediates  the  sensation  of  thirst.  The  water  taken  into  the  body  does 
not,  however,  serve  directly  as  a  source  of  energy,  since  it  is  finally  eliminated 
in  the  form  in  which  it  is  taken  in  ;  it  serves  only  to  replace  water  lost  from 
the  tissues  and  liquids  of  the  body,  and  it  furnishes  also  the  menstruum  for  the 
varied  chemical  reactions  that  take  place.  Continued  deprivation  of  water 
leads  to  intolerable  thirst,  the  cause  of  which  is  usually  referred  to  the  altered 
composition  of  the  tissues  gen  era  11  y.  including  the  peripheral  nervous  system. 

Inorganic  Suits, — The  essential  value  of  the  inorganic  salts  to  the  proper 
nutrition  of  the  body  does  not  com  moldy  force  itself  upon  our  attention,  since, 
as  a  rule,  we  get  our  proper  supply  unconsciously  with  our  food,  without  the 

sessity  of  making  a  deliberate  selection.      NaCl  (common   table-salt)  forms 

an  exception,  however,  to  this  rule.  Speaking  generally,  inorganic  salts  do 
not  serve  asa  source  of  heat-energy  to  the  body — that  is,  the  reactions  that 
they  may  undergo  are  not  accompanied  by  the  transformation  of  a  material 
amount  of  chemical  energy  into  heat.  On  the  other  hand,  their  presence  and 
distribution  by  virtue  of  their  osmotic  pressure  may  exercise  an  important 
influence  upon  the  movement  of  water  in  the  body.  Most  of  the  salts  found  in 
the  urine  and   other  excreta   are   eliminated   in   the  same  form  in  which   thev 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  355 

were  received  into  the  body,  Some  of  them,  however,  notably  the  phosphates 
and  the  sulphates,  are  formed  in  the  course  of  the  metabolism  of  the  tissues, 
and  without  doubt  reactions  of  various  kinds  occur  affecting  the  composition 
of  many  of  the  salts — for  example,  the  decomposition  of  the  chlorides  to  form 
the  HC1  of  gastric  juice.  But  these  reactions  do  not  materially  influence  the 
supply  of  energy  in  the  body :  the  value  of  the  salts  lies  in  the  general  fact 
that  they  are  necessary  to  the  maintenance  of  the  normal  physical  and  chem- 
ical properties  of  the  tissues  and  the  body-fluids.  Experimental  investigation  l 
has  shown  in  a  surprising  way  how  immediately  important  the  salts  are  in  this 
respect.  Forster  fed  dogs  and  pigeons  on  a  diet  in  which  the  saline  constit- 
uents had  been  much  reduced,  although  not  completely  removed.  The  animals 
were  given  proteids,  fats,  and  carbohydrates,  but  they  soon  passed  into  a 
moribund  condition.  It  seemed,  in  fact,  that  the  animals  died  more  quickly 
on  a  diet  poor  in  salts  than  if  they  had  been  entirely  deprived  of  food. 
Similar  experiments  were  made  by  Lunin  upon  mice,  with  corresponding 
results.  He  showed,  moreover,  that  while  mice  live  very  well  upon  cow's  milk 
alone,  yet  if  given  a  diet  almost  free  from  inorganic  salts,  consisting  of  the 
casein  and  fats  of  milk  plus  cane-sugar,  they  soon  died.  Moreover,  if  all  the 
inorganic  salts  of  milk  were  added  to  this  diet  in  the  proportion  in  which 
they  exist  in  the  ash  of  milk,  the  mixture  still  failed  to  support  life.  It  would 
seem  from  this  result  that  the  inorganic  salts  cannot  fulfil  completely  their 
proper  functions  in  the  body  unless  they  exist  in  some  special  combination 
with  the  organic  constituents  of  the  food.  In  this  connection  it  is  well  to  bear 
in  mind  that  proteids  as  they  occur  in  nature  seem  always  to  be  combined 
with  inorganic  salts,  and  the  properties  of  proteids,  as  we  know  them,  are 
undoubtedly  dependent  in  part  upon  the  presence  of  this  inorganic  constituent. 
We  may  assume  that  the  original  synthesis  of  the  organic  and  inorganic 
constituents  is  made  in  the  plant  kingdom,  and  that,  in  its  own  way, 
the  inorganic  constituent  of  the  molecule  is  as  necessary  to  the  proper 
nutrition  of  the  animal  tissues  as  is  the  organic.  One  salt  (NaCl)  is 
consumed  by  many  animals,  including  man,  in  excess  of  the  amount  uncon- 
sciously ingested  with  the  food.  Bunge  points  out  that  purely  carnivorous 
animals  are  not  known  to  crave  this  salt,  while  the  herbivora  with  some 
exceptions — for  example,  the  rabbit — take  it  at  times  largely  in  excess. 
The  need  of  salt  on  the  part  of  these  animals  is  well  illustrated  among  the 
wild  forms  by  the  eagerness  with  which  they  visit  salt-licks.  Bunge  advances 
an  ingenious  theory  to  account  for  the  difference  between  the  herbivora  and 
the  carnivora  in  regard  to  the  use  of  salt.  He  points  out  that  in  plant 
food  there  is  a  relatively  large  excess  of  potassium  salts.  When  these  salts 
enter  the  liquids  of  the  body  they  react  with  the  NaCl  present  and  a  mutual 
decomposition  ensues,  with  the  formation  of  KCl  and  the  sodium  salt  of  the 
acid  formerly  combined  with  the  potassium,  and  the  new  salts  thus  formed  are 
eliminated  by  the  kidneys  as  soon  as  they  accumulate  beyond  the  normal  limit. 

1  Bunge:   Physiological  and  Pathological  Chemistry,  translated  by  Wboldridge,  L890. 


356  AN    AMERICAN    TEXT-BOOK    OF   J'HYSIOLOGY. 

In  this  way  the  normal  proportion  of  NaCl  in  tli£  tissues  and  the  body-fluids 
is  lowered  and  a  craving  for  the  Bait  is  produced.  Bunge  states  that  it  has  been 
shown  among  men  that  vegetarians  habitually  consume  more  salt  than  those 
who  are  accustomed  to  eat  meats.  The  salts  of  calcium  and  of  iron  have  also 
a  special  importance  that  needs  a  word  of  reference.  The  particular  import- 
ance of  the  iron  salts  lies  in  their  relation  to  haemoglobin.  The  continual 
formation  of  new  red  blood-corpuscles  in  the  body  requires  a  supply  of  iron 
Baits  for  the  synthesis  of  the  haemoglobin,  and,  although  there  is  a  probability 
(see  p.  323)  that  the  iron  compound  of  the  disintegrating  corpuscles  is  again 
used  in  part  for  this  purpose,  we  must  suppose  that  the  body  requires  addi- 
tional iron  in  the  food  from  time  to  time  to  take  the  place  of  that  which  is 
undoubtedly  lost  in  the  excretions.  It  has  been  shown  that  iron  is  contained 
in  animal  and  vegetable  foods  in  the  form  of  an  organic  compound,  and  the 
evidence  at  hand  goes  to  show  that  only  when  it  is  so  combined  can  the  iron 
be  absorbed  readily  and  utilized  in  the  body,  while  the  efficacy  of  the  inor- 
ganic salts  of  iron  as  furnishing  directly  a  material  for  the  production  of  haemo- 
globin is,  to  say  the  least,  open  to  doubt.  Bunge  isolated  from  the  yolk  of 
eggs  an  iron-containing  nuclei n  which  he  calls  hcematogen,  because  in  the 
developing  lien's  e<i^  it  is  the  only  source  from  which  the  iron  required 
for  the  production  of  haemoglobin  can  be  obtained.  It  is  possible  that  sim- 
ilar compounds  occur  in  other  articles  of  food.  Most  of  the  iron  taken  with 
food,  however,  including  that  present  in  the  haemoglobin  of  meats,  passes 
out  in  the  feces  unabsorbed.  It  is  probable  that  there  is  an  actual  excre- 
tion of  iron  from  the  body,  and,  so  far  as  known,  this  excretion  is  effected 
in  small  part  through  the  urine  and  bile,  but  mainly  through  the  walls  of  the 
intestine, the  iron  being  eliminated  finally  in  the  feces.  The  large  proportion 
of  calcium  Baits  found  in  the  skeleton  implies  a  special  need  of  these  salts  in 
the  food,  particularly  in  that  of  the  young.  It  has  been  shown  that  if  young 
dogs  are  i'ed  upon  a  diet  p  >or  in  Ca  salts,  the  bones  fail  to  develop  properly, 
and  a  condition  similar  to  rickets  in  children  becomes  apparent.  In  addition 
to  their  relations  to  bone-formation  and  the  fact  that  they  form  a  normal  con- 
stituent of  the  tissues  and  liquids  of  the  body,  calcium  salts  are  necessary  to 
the  coagulation  of  blood  (see  p.  57),  and,  moreover,  they  seem  to  be  connected 
in  some  intimate  way  with  the  rhythmic  contractility  of  heart-muscle,  and, 
indeed,  with  the  normal  activity  of  protoplasm  in  general,  animal  as  well  as 
plant.  Notwithstanding  the  special  importance  of  calcium  in  the  body,  no 
great  amount  of  it  seems  to  be  normally  absorbed  or  excreted.  Voit  bas 
shown  that  the  calcium  eliminated  from  the  body  is  excreted  mainly  through 
the  intestinal  walls,  but  that  most  of  the  Ca  in  the  feces  is  the  unabsorbed  (a 
of  the  food.  It  is  possible  that  the  Ca  must  be  present  in  some  special  com- 
bination in  order  to  be  absorbed  and  utilized  in  the  body.  A  point  of  special 
interest  in  connection  with  the  nutritive  value  of  the  inorganic  salts  was  brought 
out  bv  Bunge  in  some  analyses  of  the  body-ash  of  sucking  animals  in  com- 
parison   with   analyses  of  the   milk   and    the   blood    of  the   mother.      In   the 


CHEMISTRY   OF  DIGESTION  AND   NUTRITION.  357 

case  of  the  dog  he  obtained  the  following  results  (mineral   constituents  in 
100  parts  of  ash) : 

Young  Pup.  Dog's  Milk.  Dog's  Serum. 

K20 8.5  10.7  2.4 

Na20 8.2                             6.1  52.1 

CaO 35.8  34.4  2.1 

MgO 1.6                             1.5  0.5 

F203 0.34                          0.14  0.12 

P205 39.8  37.5  5.9 

CI 7.3  12.4  47.6 

The  remarkable  quantitative  resemblance  between  the  ash  of  milk  and  the 
ash  of  the  body  of  the  young  indicates  that  the  inorganic  constituents  of  milk 
are  especially  adapted  to  the  needs  of  the  young;  while  the  equally  striking 
difference  between  the  ash  of  milk  and  the  ash  of  the  maternal  blood  seems  to 
show  that  the  inorganic  salts  of  milk  are  formed  from  the  blood-serum  not 
simply  by  diffusion,  but  rather  by  some  selective  secretory  act.  These  facts 
come  out  most  markedly  in  connection  with  the  CaO  and  the  P205.  For 
further  details  as  to  the  history  of  calcium  and  iron  in  the  body,  consult  the 
section  on  Chemistry  of  the  Body,  under  calcium  and  iron. 

I.  Accessory  Articles  of  Diet  ;  Variations  of  Body-metabolism 
under  Different  Conditions  ;  Potential  Energy  of  Food  ; 
Dietetics. 
Accessory  Articles  of  Diet. — By  accessory  articles  of  diet  we  mean  those 
substances  that  are  taken  with  food,  not  for  the  purpose  of  replacing  tissue  or 
yielding  energy,  but  to  add  to  the  enjoyment  of  eating,  to  stimulate  the  appetite, 
to  aid  in  digestion  and  absorption,  or  for  some  other  subsidiary  purpose.  They 
include  such  things  as  the  condiments  (mustard,  pepper,  etc.),  the  flavors,  and 
the  stimulants  (alcohol,  coffee,  tea,  chocolate,  beef-extracts).  They  all  possess, 
undoubtedly,  a  positive  nutritive  or  digestive  value  beyond  contributing  to  the 
mere  pleasures  of  the  palate,  but  their  importance  is  of  a  subordinate  character 
as  compared  with  the  so-called  alimentary  principles.  They  may  be  omitted 
from  the  diet,  as  happens  or  may  happen  in  the  ease  of  animals,  without 
affecting  injuriously  the  nutrition  of  the  body,  although  it  is  probable  tli.it 
neither  man  nor  the  lower  animals  would  voluntarily  eat  food  entirely  devoid 
of  flavor. 

Stimulants. — The  well-known  stimulating  effect  of  alcohol,  tea,  coffee,  etc.,  is 
generally  attributed  to  a  specific  action  on  the  nervous  system  whereby  the  irri- 
tability of  the  tissue  is  increased.  The  physiological  effect  of  tea,  coffee,  and 
chocolate  is  due  to  the  alkaloids  callein  (triinetliyl-xanthin)  and  thcobromin 
(dimethyl-xanthin).  In  small  doses  these  substances  are  oxidized  in  the 
body  and  yield  a  corresponding  amount  of  energy,  but  their  value  from  this 
standpoint  is  altogether  unimportant  compared  with  their  act  ion  as  stimulants. 
Alcohol  also,  when  not  taken  in  too  large  quantities,  may  be  oxidized  in  the 
body  and  furnish  a  not  inconsiderable  amount  of  energy.  It  is,  however,  a 
matter  of  controversy  at  present  whether  alcohol  in  small  doses  can  be  con- 


358  AN  AMERICA  X    TEXT- BO  OK    OF  PHYSIOLOGY. 

sidered  a  true  food-stuff,  capable  of  replacing  a  corresponding  amount  of  fats 
or  of  carbohydrates  in  the  daily  diet.  The  evidence  is  partly  for  and  partly 
againsl  such  a  use  of  alcohol.  A  number  of  observers'  contend 
that  when  the  body  is  brought  into  a  condition  of  nitrogenous  equilib- 
rium on  a  given  diet  of  proteids,  hits,  and  carbohydrates,  and  a  certain  pro- 
portion  of  the  carbohydrates  or  fats  is  then  replaced  by  an  isodynamic 
amount  of  alcohol — that  is,  by  an  amount  of  alcohol  that  on  combustion  would 
yield  the  same  amount  of  heat — the  body  does  not  remain  in  nitrogenous  equi- 
librium, but,  on  the  contrary,  loses  in  nitrogen,  thus  indicating  that  the  oxida- 
tion of  alcohol  in  the  body  does  not  protect  the  proteid  from  consumption  as 
in  the  case  of  the  non-nitrogenous  food-stuffs,  fats,  and  carbohydrates. 
Miura,  for  example,  brought  himself  into  a  condition  of  nitrogen  equilibrium 
upon  a  mixed  diet.  Then  for  a  certain  period  a  portion  of  the  carbohydrates 
was  omitted  from  the  diet  and  its  place  substituted  by  an  isodynamic  amount 
of  alcohol.  The  result  was  a  loss  of  proteid  from  the  body,  showing  that  the 
alcohol  had  not  protected  the  proteid  tissue  as  it  should  have  done  if  it  acts 
as  a  food.  In  a  third  period  the  old  diet  was  resumed,  and  after  nitrogen 
equilibrium  had  again  been  established  the  same  proportion  of  carbohydrate 
was  omitted  from  the  diet,  but  alcohol  was  not  substituted.  When  the  diet 
was  poor  in  proteid,  it  was  found  that  less  proteid  was  lost  from  the  body  when 
the  alcohol  was  omitted  than  when  it  was  used,  indicating  that,  so  far  from 
protecting  the  proteid  of  the  body  by  its  oxidation,  the  alcohol  exercised  a 
directly  injurious  effect  upon  proteid-consumption.  Atwater,2  on  the  con- 
trary,  as  the  result  of  elaborate  experiments  in  which  the  heat  production  was 
determined  calorimetrically  and  the  body  metabolism  was  determined  also 
from  an  examination  of  the  excreta,  finds  that  alcohol,  when  substituted  for 
the  non-nitrogenous  food-stuffs,  does  protect  the  proteid  of  the  body  from 
consumption  just  as  the  fats  and  carbohydrates  do,  and  is,  therefore,  entitled 
scientifically  to  the  designation  of  a  food-stuff.  So  also  Geppert  and  Zuntz 
found  that  alcohol  in  small  doses  caused  no  increase  in  the  oxygen  consumed, 
in  spite  of  the  fact  that  it  was  burnt  in  the  body;  the  supposition  in  this 
case  was  that  the  burning  of  the  alcohol  saved  some  of  the  body  material  from 
consumption.  Numerous  other  researches  might  be  quoted  to  show  that  the 
effect  of  moderate  quantities  of  alcohol  upon  body-metabolism  is  not  yet  satis- 
factorily understood.  Before  making  any  positive  statements  as  to  the  details 
of  its  action  it  is  wise,  therefore,  to  wait  until  reliable  experimental  results 
have  accumulated.  The  specific  action  of  alcohol  on  the  heart,  stomach,  and 
other  organs  has  been  investigated  more  or  less  completely,  but  the  literature 
is  too  greaf  and  the  results  are  too  uncertain  to  permit  any  extended 
resume  to  be  given  here.  When  alcohol  is  taken  in  excess  it  produces  the 
familiar  symptoms  of  intoxication,  which  may  pass  subsequently  into  a  con- 
dition of  stupor   or  even   death,  provided   the   quantity  taken  is  sufficiently 

1  Zefochrift  f.  Uin.  Medicin,  1892,  Bel.   xx.  8.  1M7.     See  also  Rosemann  :  Archiv  fur  die  ges- 
ammte  Physiologic,  1899,  Bd.  77,  S.  40."),  for  references. 

2  American  Journal  of  Physiology,  1900,  vol.  3,  p.  xii. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  359 

great.  So,  also,  the  long-continued  use  of  alcohol  in  large  quantities  is  known 
to  produce  serious  lesions  of  the  stomach,  liver,  nerves,  blood-vessels,  and 
other  organs.  As  has  been  stated  before,  alcohol  is  absorbed  easily  from  the 
stomach  and  seems  to  increase  the  absorption  of  other  soluble  substances.1 
Upon  the  digestive  action  of  the  proteolytic  and  anxiolytic  enzymes  alcohol 
in  certain  strengths  has  a  retarding  effect,  but  in  small  percentages  its  action 
is  not  noticeable.2  Upon  the  secretion  of  saliva  and  gastric  juice  it  has  a  dis- 
tinct stimulating  action,3  and  its  action  as  a  general  stimulant  to  the  central 
nervous  system  is  indicated  by  its  effect  on  the  reaction  time,  and  under 
certain  conditions  upon  muscular  exertion  as  measured  by  the  ergograph.4 
The  effect  of  alcohol  upon  the  body  evidently  varies  greatly  with  the  quan- 
tity used.  It  may  perhaps  be  said  with  safety  that  in  small  quantities  it  is 
beneficial,  or  at  least  not  injurious,  barring  the  danger  of  acquiring  an  alcohol 
habit,  while  in  large  quantities  it  is  directly  injurious  to  various  tissues. 

Condiments  and  Flavors. — These  substances  probably  have  a  directly  bene- 
ficial effect  on  the  processes  of  digestion  by  promoting  the  secretion  of  saliva, 
gastric  juice,  etc.,  in  addition  to  the  important  fact  that  they  increase  thepal- 
atableness  of  food,  and  hence  increase  the  desire  for  food  and  the  secretion 
of  the  gastric  juice.  With  reference  to  the  condiments,  Brandl  has  shown 
that  mustard  and  pepper  also  markedly  increase  the  absorption  of  soluble 
products  from  the  stomach. 

Beef-tea,  Meat-extracts. — The  recent  experiments  of  Pawlow  and  his  co- 
workers (see  section  on  Secretion)  have  shown  that  these  substances  have  a 
specific  value  in  their  stimulating  effect  upon  the  gastric  glands.  They  appear 
to  contain  substances  that  act  as  definite  secretogogues  toward  these  glands. 

Conditions  Influencing  Body-metabolism. — In  considering  the  influence 
of  the  various  food-stuffs  upon  body-metabolism  we  have  for  the  most  part 
neglected  to  mention  the  effect  of  changes  in  the  condition  of  the  body.  It 
goes  without  saying  that  such  things  as  muscular  work,  sleep,  variations  in 
temperature,  etc.  have  or  might  have  an  important  effect  upon  the  character 
and  amount  of  the  chemical  changes  going  on  in  the  body,  and  in  conse- 
quence a  great  many  elaborate  investigations  have  been  made  to  ascertain  pre- 
cisely the  effect  of  conditions  such  as  those  mentioned  upon  the  amount  of 
the  excretions,  the  production  of  heat  in  the  body,  and  other  similar  points 
which  throw  light  upon  the  nature  of  the  metabolic  processes. 

Effect  of  Muscular  Work. — It  is  a  matter  of  common  knowledge  that  mus- 
cular work  increases  the  amount  of  food  consumed,  and  then  lore  the  total 
body-metabolism,  but  it  has  been  a  point  in  controversy  whether  the  increased 
oxidations  affect  the  proteid  or  the  non-proteid  material.  According  (<>  Liebig, 
the  source  of  the  energy  of  muscular  work  lies  in  the  metabolism  of  the  proteid 
constituents,  and  with  increased  muscular  work   there  should  be  increased  de- 

1  Brandl  :  Zeitschrift  fur  Biologie,  L892,  Bd.  29,  S.  277. 

2  Chittenden  and  Mendel :  American  Journal  of  the  Medical  Sciences,  1896. 

:i  Chittenden,  Mendel  and  Jackson:  American  Journal  of  Physiology,  1898,  vol.  i.  p.  164. 
4  Schuniberg:  Archiv  fur  Physiologic,  1899,  Suppl.  Bd.  S.  289. 


360  AN   AMERICAN    TEXT- BOOK    OF  PHYSIOLOGY. 

struction  of  proteid  and  an  increase  in  the  nitrogenous  excretions.  That  the 
total  energy  of  muscular  work  is  not  derived  from  the  oxidation  or  metabolism 
of  proteid  alone  was  clearly  demonstrated  by  the  famous  experiment  of  Fick 
and  Wislicenus.  These  physiologists  ascended  the  Faulhorn  to  a  height  of 
1956  meters.  Knowing  the  weight  of  his  body,  each  could  estimate  how  much 
work  was  done  in  ascending  such  a  height.  Kick's  weight,  for  example,  was 
66  kilograms,  therefore  in  climbing  the  mountain  he  performed  66  X  1956  = 
129,096  kilogrammeters  of  work.  In  addition,  the  work  of  the  heart  and  the 
respiratory  muscles,  which  could  not  be  determined  accurately,  was  estimated 
at  30,000  kilogrammeters.  There  was,  moreover,  a  certain  amount  of  muscular 
work  performed  in  the  movements  of  the  arms  and  in  walking  upon  level 
ground  that  was  omitted  entirely  from  their  calculations.  For  seventeen  hours 
before  the  ascent,  during  the  climb  of  eight  hours,  and  for  six  hours  afterward 
their  food  was  entirely  non-nitrogenous,  so  that  the  urea  eliminated  came  entirely 
from  the  proteid  of  the  body.  Nevertheless,  when  the  urine  was  collected  and 
the  urea  estimated  it  was  found  that  the  potential  energy  contained  in  the  pro- 
teid destroyed  wasentirely  insufficient  to  account  for  the  work  done.  Although 
later  estimates  would  modify  somewhat  the  actual  figures  of  their  calculation, 
the  margin  was  so  great  that  the  experiment  has  been  accepted  as  showing 
conclusively  that  the  total  energy  of  muscular  work  does  not  come  necessarily 
from  the  oxidation  of  proteid  alone.  Later  experiments  made  by  Voit  upon 
a  dog  working  in  a  tread- wheel  and  upon  a  man  performing  work  while  in  the 
respiratorv  chamber  (p.  344)  gave  the  surprising  result  that  not  only  may  the 
energy  of  muscular  work  be  far  greater  than  the  potential  energy  of  the  proteid 
simultaneously  oxidized,  but  that  the  performance  of  muscular  work  within 
certain  limits  does  not  affect  at  all  the  amount  of  proteid  metabolized  in  the 
body,  since  the  output  of  urea  is  the  same  on  working-days  as  during  days  of 
rest.  Careful  experiments  by  an  English  physiologist,  Parkes,  made  upon 
soldiers  while  resting  and  after  performing  long  marches  showed  also  that 
there  is  no  distinct  increase  in  the  excretion  of  urea  after  muscular  exercise. 
It  followed  from  these  experiments  thai  Liebig's  theory  as  to  the  source  of 
the  energy  of  muscular  work  is  incorrect,  and  that  the  increase  in  the  oxida- 
tions in  the  body  that  undoubtedly  occurs  during  muscular  activity  must 
affect  only  the  non-proteid material,  that  is,  the  fats  and  carbohydrates.  More 
recently  the  question  was  reopened  by  experiments  made  under  Pfluger 
by  Argutinsky. '  In  these  experiments  the  total  nitrogen  excreted  was  deter- 
mined with  especial   care  in   the  sweat   as  well  as  in  the  urine  and   the  feces. 

The    muscular   work    d consisted    in    long   walks   and    mountain-climbs. 

Argutinsky  found  that  work  caused  a  marked  increase  in  the  elimination  of 
nitrogen,  the  increase  extending  over  a  period  of  three  days,  and  he  estimated 
that  the  additional  proteid  metabolized  in  consequence  of  the  work  was  suf- 
ficient to  account  for  most  of  the  energy  expended  in  performing  the  walks 
and  climbs.  A  number  of  objections  have  been  made  to  Argutinsky 's  work. 
It  has  been  asserted  that  during  his  experiment  he  kept  himself  upon  a 
!  Pfluger^  Archiv  fur  die  gesammte  Physiologie,  1890,  vol.  46,  p.  552. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  361 

diet  deficient  in  non-proteid  material;  that  if  the  supply  of  this  material  had 
been  sufficient,  none  of  the  additional  proteid  would  have  been  oxidized.  It 
must  be  admitted,  however,  that  the  experiments  of  A.rgutinsky  compel  us  to 
state  the  proposition  above  as  to  the  relation  between  muscular  work  and 
proteid  metabolism  in  a  more  careful  way.  It  is  necessary  to  modify  the 
statement  generally  made  to  the  extent  of  saying  that  muscular  work  causes 
no  increase  in  proteid  metabolism,  provided  the  supply  of  non-nitrogenous 
food  is  abundant. 

If  now  we  compare  the  amounts  of  C02  eliminated  during  work  and  during 
rest,  it  will  be  found  that  there  is  a  very  decided  increase  during  work.  In  the 
experiments  made  by  Pettenkofer  and  Voit  the  0O2  given  off  by  a  man 
during  a  day  of  muscular  work  was  nearly  double  that  eliminated  during  a 
resting-day.  Indeed,  the  same  fact  has  been  observed  repeatedly  upon  isolated 
muscles  made  to  contract  by  artificial  stimuli.  Assuming,  then,  that  muscular 
work  causes  no  increase  in  the  nitrogen  excreted,  but  a  marked  increase  in  the 
C02  eliminated,  we  are  justified  iu  saying  that  the  energy  of  muscular  work 
under  normal  conditions  comes  mainly,  if  not  exclusively,  from  the  oxidation 
of  non-proteid  material.  The  machine  that  does  the  work,  the  muscle,  is 
par  excellence  a  proteid  tissue,  but  the  normal  resting  metabolism  of  its  pro- 
teid substance  is  not  increased  by  the  chemical  changes  of  contraction.  Or, 
to  put  it  in  another  way,  the  chemical  changes  that  give  rise  to  the  energy  lib- 
erated in  contraction  may  involve  only  the  non-proteid  material.  It  is  inter*  >t- 
ing  to  remember  in  this  connection  that  the  consumption  of  glycogen,  or  of 
the  sugar  derived  from  it,  is  intimately  connected  with  muscular  work.  The 
glycogen  of  the  body  in  an  animal  deprived  of  food  disappears  much  more 
rapidly  if  the  animal  is  made  to  work  his  muscles  than  if  he  remains  at 
rest.  In  an  experiment  by  Kiilz  upon  well-fed  dogs  it  was  found  that  the 
glycogen  was  practically  all  used  up  in  a  single  fasting-day  during  which  the 
animals  did  a  great  deal  of  work.  Morat  and  Dufourt  have  shown  also  that 
a  muscle  after  prolonged  contraction  takes  much  more  sugar  from  the  blood  than 
it  did  previous  to  the  contraction,  and  Harley1  finds  that  power  to  perform 
muscular  work  may  be  increased  and  susceptibility  to  fatigue  be  diminished 
by  eating  sugar  in  quantities.  It  is,  in  fact,  generally  agreed  that  glycogen  i- 
used  up  in  muscle-contractions,  but  the  way  in  which  the  destruction  of  the 
glycogen  is  effected  is  not  definitely  known.  After  the  glycogen  has  been  con- 
sumed it  is  probable  that  the  other  constituents  of  the  body,  the  fats  and  the 
proteids,  are  called  upon  to  furnish  the  necessary  energy.  I'd-  this  reason 
we  should  expect,  in  a  person  performing  excessive  muscular  work,  that  there 
would  be  an  increased  destruction  of  proteid  when  the  supply  of  aon-proteid 
food  is  insufficient. 

Metabolism  during  Sleep. —  It  has  been  shown  that  during  sleep  there  is  no 

marked  diminution  of  the  nitrogen  excreted,  and  therefore  no  distincl  decrease 

in   the    proteid    metabolism;    on    the    contrary,   the   <  '<  >2  eliminated   and    the 

oxygen   absorbed   are   unquestionably  diminished.     This  latter  fact    finds   its 

1  Journal ,,/  Physiology,  1894,  vol.  xvi.  j>.  '.'7. 


362  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

simplest  explanation  in  the  supposition  that  the  muscles  are  less  active  during 
sl<  ep.  The  muscles  do  less  work  in  the  way  of  contractions,  and,  in  addition, 
probably  suffer  a  diminution  in  tonicity  which  also  affects  their  total  metab- 
olism. 

Effect  of  Valuations  in  Temperature. — In  warm-blooded  animals  variations 
of  outside  temperature  within  ordinary  limits  do  not  affect  the  body-tem- 
perature.  A  full  account  of  the  means  by  which  this  regulation  is  effected 
will  be  found  in  the  section  upon  Animal  Heat.  So  long  as  the  temper- 
ature of  the  body  remains  constant,  it  has  been  found  that  a  fall  of  outside 
temperature  may  increase  the  oxidation  of  non-proteid  material  in  the  body, 
the  increase  being  in  a  general  May  proportional  to  the  fall  in  temperature. 
That  the  increased  oxidation  affects  the  non-proteid  constituents  is  shown  by 
the  fact  that  the  urea  remains  unchanged  in  quantity,  other  conditions  being  the 
same,  while  the  oxygen-consumption  and  the  C02-elimination  are  increased. 
This  effect  of  temperature  upon  the  body-metabolism  is  due  mainly  to  a  reflex 
stimulation  of  the  motor  nerves  to  the  muscles.  The  temperature-nerves  of 
the  skin  are  affected  by  the  fall  in  outside  temperature,  and  bring  about 
reflexly  an  increased  or  a  diminished  innervation  of  the  muscles  of  the  body. 
Indeed,  it  is  stated1  that  unless  the  lowering  of  the  temperature  is  sufficient 
to  cause  shivering  or  muscular  tension  no  increase  in  the  C02-excretion  results. 
This  fact  suffices  to  explain,  therefore,  the  physiological  value  of  shivering 
and  muscular  restlessness  when  the  outside  temperature  is  low.  The  fact  that 
variations  in  outside  temperature  affect  only  the  consumption  of  non-proteid 
material  falls  in,  therefore,  with  the  conception  of  the  nature  of  the  metab- 
olism of  muscle  in  activity,  given  above.  When  the  means  of  regulating 
the  body-temperature  break  down  from  too  long  an  exposure  to  excessively 
low  or  excessively  high  temperatures,  the  total  bodv-mPtabolism,  proteid 
as  well  as  non-proteid,  increases  with  a  rise  in  body-temperature  and  de- 
creases with  a  fall  in  temperature.  In  fevers  arising  from  pathological 
causes  it  has  been  shown  that  there  is  also  an  increased  production  of  urea  as 
well  as  of  C02. 

Effect  of  Starvation. — A  starving  animal  must  live  upon  the  material  pres- 
ent in  its  body.  This  material  consists  of  the  fat  stored  up,  the  circulating 
and  tissue  proteid,  and  the  glycogen.  The  latter,  which  is  present  in  compara- 
tively small  quantities,  is  quickly  used,  disappearing  more  or  less  rapidly 
according  to  the  extent  of  muscular  movements  made,  although  in  any  case  it 
practically  vanishes  in  a  few  days.  Thereafter  the  animal  lives  on  its  own 
proteid  and  fat,  and  if  the  starvation  is  continued  to  a  fatal  termination  the 
body  becomes  correspondingly  emaciated.  Examination  of  the  several  tissues 
in  animals  starved  to  death  has  brought  out  some  interesting  facts.  Voit  took 
two  cats  of  nearly  equal  weight,  fed  them  equally  for  ten  days,  and  then  killed 
one  to  serve  as  a  standard  of  comparison  and  starved  the  other  for  thirteen 
days:  the  latter  animal  lost  1017  grams  in  weight,  and  the  loss  was  divided  as 
follows  among  the  different  organs : 

1  Johannson:  Skandinavisehr*  Archiv  fiir  Physioloyie,  1897,  Kd.  vii.  S.  123. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  363 

Supposed  wt.  of             Actual  loss  of  Loss  to  each  100  grams 

organs  before  organs  in  of  fresh  organ 

starvation.  grams.  (percentage  loss). 

Bone 393.4  54.7  13.9 

Muscle 1408.4  429.4  30.5 

Liver 91.9  49.4  53.7 

Kidney 25.1  6.5  25.9 

Spleen 8.7  5.8  66.7 

Pancreas 6.5  1.1  17.0 

Testes 2.5  1.0  40.0 

Lungs 15.8  2.8  17.7 

Heart 11.5  0.3  2.6 

Intestines 118.0  20.9  18.0 

Brain  and  cord  ....         40.7  1.3  3.2 

Skin  and  hair     ....      432.8  89.3  20.6 

Fat 275.4  267.2  97.0 

Blood 138.5  37.3  27.0 

Remainder 136.0  50.0  36.8 

According  to  these  results,  the  greatest  absolute  loss  was  in  the  muscles  (429 
grams),  while  the  greatest  percentage  loss  was  in  the  fat  (97  percent.),  which 
had  practically  disappeared  from  the  body.  It  is  very  significant  that  the 
central  nervous  system  and  the  heart,  organs  which  we  may  suppose  were  in 
continual  activity,  suffered  practically  no  loss  of  weight  :  they  had  lived  at 
the  expense  of  the  other  tissues.  We  must  suppose  that  in  a  starving  animal 
the  fat  and  the  proteid  material,  particularly  that  of  the  voluntary  muscles, 
pass  into  solution  in  the  blood,  and  are  then  used  to  nourish  the  tissues  gen- 
erally and  to  supply  the  heat  necessary  to  maintain  the  body-temperature. 
Examination  of  the  excreta  in  starving  animals  has  shown  thai  a  greater 
quantity  of  proteid  is  destroyed  during  the  first  day  or  two  than  in  the  sub- 
sequent days.  This  fact  is  explained  on  the  supposition  that  the  body  i>  al 
first  richly  supplied  with  "  circulating  proteid  "  derived  from  its  previous 
food,  and  that  after  this  is  metabolized  the  animal  lives  entirely,  so  far  as 
proteid-consumption  is  concerned,  upon  its  "tissue  proteid."  If  the  animal 
remains  quiet  during  starvation,  the  amount  of  nitrogen  excreted  daily  soon 
reaches  a  nearly  constant  minimum,  showing  that  a  practically  constant 
amount  of  proteid  (together  with  fat)  is  consumed  daily  to  furnish  body-heat, 
and  probably  to  repair  tissue  waste  in  the  active  organs,  such  as  the  heart. 
Shortly  before  death  from  starvation  the  daily  amount  of  proteid  consumed 
may  increase,  as  shown  by  the  larger  amount  of  nitrogen  eliminated.  This 
fact  is  explained  by  assuming  that  the  body  fat  is  then  exhausted  and  the 
animal's  metabolism  is  confined  to  the  tissue  proteids  alone.  The  general 
fact  that  the  loss  of  proteid  is  greatest  during  the  firsl  one  or  two  days  of 
starvation  lias  been  confirmed  recently  upon  men,  in  a  number  of  interesting 
experiments  made  upon  professional  tasters.       For  the  numerous  details  as  to 

loss  of  weight,  variations  of  temperature,  etc.,  carefully   r< rded    in    these 

latter  experiments,  reference  must  be  made  to  original  sources.'  It  may  be 
added,  in  conclusion,  that  the  fatter  the  body  is  to  begin  with,  the  longer  will 

1  Yirchow's  Arehiv,  lid.  131,  supplement,  1893,  and  Luciani,  Das  ffungern,  1S90. 


364  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

starvation  be  endured,  and  if  water  is  consumed  freely  the  evil  effects  of  star- 
vation, as  well  as  the  disagreeable  sensations  of  hunger,  are  very  much 
reduced. 

Potential  Energy  of  Food. — The  chemical  changes  occurring  in  the  body 
are  accompanied  by  a  transformation  of  chemical  energy  to  different  forms — 
for  example,  to  heat,  electricity,  and  mechanical  work.  By  far  the  most  of  this 
energy  takes  the  form,  directly  or  indirectly,  of  heat  Even  when  the  muscles 
are  apparently  at  rest  we  know  that  theyare  undergoing  chemical  changeswhich 
give  risetoheat.  When  :t  muscle  contracts, the  greater  part  (four-fifths)  of  th< 
energy  liberated  by  the  chemical  change  takes  the  form  of  heat ;  a  much  smallei 
part  (al)ont  one-fifth  as  a  maximum)  may  perform  mechanical  work,  which 
in  turn,  as  in  the  case  of  the  respiratory  muscles  and  the  heart,  may  be  con- 
verted to  heat  within  the  body.  Roughly  speaking,  an  adult  man  gives  off 
from  his  body  in  the  course  of  twenty-four  hours  about  2,400,000  calories  of 
heat  (1  calorie  =  the  heat  uecessary  to  raise  1  cubic  centimeter  of  water  1°  C). 
This  supply  of  heat  is  derived  from  the  metabolism  or  physiological  oxidation 
of  the  proteids,  the  fats,  and  the  carbohydrates  that  we  take  into  the  body  in 
our  food.  By  means  of  the  oxygen  absorbed  through  the  lungs  these  substances 
are  burnt,  with  the  formation  of  C02,  H20,  and  urea  or  some  similar  nitrog- 
enous waste  product.  In  the  long  run,  then,  the  source  of  body-energy  is  found 
in  the  potential  energy  contained  in  our  food.  Our  energy-yielding  foods — 
proteids,  fats,  and  carbohydrates — are  more  or  less  complex  bodies  that  are 
built  up  originally  by  plant  organisms  with  the  aid  of  solar  energy;  when 
they  are  burnt  or  otherwise  destroyed,  with  the  formation  of  simpler  bodies 
(such  as  C02  or  H20),  their  so-called  potential  energy  is  liberated  in  the 
form  of  heat,  and  this  is  what  occurs  in  the  body.  From  the  standpoint  of  the 
law  of  conservation  of  energy  it  is  easy  to  understand  that  the  amount  of 
available  energy  in  any  food-stuff  may  be  determined  by  burning  it  outside  the 
body  and  measuring  the  quantity  of  heat  liberated.  If  a  gram  of  sugar  is 
burnt,  it  is  converted  to  C02  and  FLO  and  a  certain  quantity  of  heat  is  liber- 
ated;  if  the  same  gram  of  sugar  had  been  taken  into  the  body,  it  would  event- 
ually have  been  reduced  to  the  form  of  C02  and  H20,  and  the  total  quantity 
of  heat  liberated  would  have  been  the  same  as  in  the  combustion  outside  the 
body,  although  the  destruction  of  the  sugar  in  the  body  may  not  be  a  direct, 
but  an  indirect,  oxidation;  that  is,  the  oxygen  may  first  be  combined  with  sugar 
and  other  food-stuffs  to  form  a  complex  molecule  which  afterward  dissociates 
into  simpler  compounds  similar  to  those  obtained  by  direct  oxidation,  or  there 
may  be  first  a  dissociation  or  cleavage  followed  by  oxidation  of  the  dissociation 
products.  In  determining  the  total  energy  given  to  the  body  we  need  only 
consider  the  form  in  which  a  substance  enters  the  body  and  the  form  in  which 
it  is  finally  eliminated.  In  the  case  of  proteids  the  combustion  in  the  body  is 
not  so  complete  as  it  is  outside  ;  the  chief  final  products  are  C02,  H20,  and 
urea.  The  urea,  however,  .-till  contains  potential  energy  which  may  be  lib- 
erated by  combustion,  and  in  determining  the  energy  of  proteid  available  to 
the  body,  that  which  is  lost  in  the  urea  must  be  deducted.  As  a  matter  of 
fact,  it  is  possible  that  the  proteid  in  the  body  is  completely  oxidized  to  C02, 


CHEMISTRY  OF  DIGESTION  AND    NUTRITION.  365 

H..O,  and  NH3 ;  but,  since  the  XH,in  this  case  is  recombined  to  form  an  ammo- 
nium compound,  and  this  in  turn  is  converted  into  urea, the  additional  energy  lib- 
erated in  the  first  combustion  is  balanced  by  that  absorbed  in  the  synthetic  produc- 
tion of  the  urea.  Thepotential  energy ofthe  fats, carbohydrates, and  proteids  can 
be  determined  by  combustion  outside  the  body;  the  energy  liberated  is  meas- 
ured in  terms  of  heat  by  some  form  of  calorimeter,  and  the  quantity  of  heat  so 
obtained,  expressed  in  calories,  is  known  usually  as  the  "combustion  equiva- 
lent." To  be  perfectly  accurate,  each  particular  form  of  fat,  proteid,  etc. 
should  be  burnt  and  its  energy  be  determined,  but  usually  average  figures  are 
employed,  as  the  amount  of  heat  given  off  by  the  different  varieties  of  any  one 
food-stuff — proteids,  for  example — does  not  vary  greatly.  According  to  Stoh- 
mann,  1  gram  of  beef  deprived  of  fat  =  5641  calories,  while  1  gram  of  veal 
gives  5663  calories.  For  muscle  extracted  with  water,  Rubner  obtained  the 
following  figures:  1  gram  =  5778  calories.  The  combustion  equivalent  of  urea 
(Rubner)  is  2523  calories.  Since  1  gram  of  proteid  yields  about  one-third  of 
a  gram  of  urea,  we  should  deduct  841  calories  from  the  combustion  equiva- 
lent of  one  gram  of  proteid  to  get  its  available  energy  to  the  body  :  5778 — 
841=4937  calories.  Practically,  however,  this  value  is  found  to  be  too  high. 
Direct  determinations  upon  the  body  in  a  calorimeter  gave  to  Rubner  the  fol- 
lowing values,  which  seem  to  be  generally  adopted  by  workers  in  this  field: 
1  gram  of  proteid=4100  calories,  1  gram  of  fat=9300  calories,  1  gram  of  carbo- 
hvdrate=4100  calories.  Weight  for  weight,  fat  contains  the  most  energy,  and, 
as  we  know,  in  cold  weather  and  in  cold  climates  the  proportion  of  fat  in  the 
food  is  increased.  In  dietetics,  however,  the  use  of  fatis  limited  by  thedifficulty 
attending  its  digestion  and  absorption  as  compared  with  carbohydrates.  Fats 
and  carbohydrates  have  the  same  general  nutritive  value  to  the  body :  they 
serve  to  supply  energy.  Since  the  amount  of  potential  energy  contained  in 
each  of  these  substances  may  be  determined  accurately  by  means  of  its  com- 
bustion equivalent,  it  would  seem  probable  that  they  might  be  mutually 
interchangeable  in  dietetics  in  the  ratio  of  their  combustion  equivalents. 
Such,  in  fact,  is  the  case.  The  ratio  of  interchange  is  known  as  the  "  i so- 
dynamic  equivalent,"  and  it  is  given  usually  as  1  :  2,4  or  2.2  ;  that  is,  fats 
may  replace  over  twice  their  weight  of  carbohydrate  in  the  diet.  It  follows 
from  the  general  principles  just  stated  that  if  we  wished  to  know  the  amount 
of  heat  produced  in  the  body  in  a  given  time,  say  twenty-lour  hours,  we  might 
ascertain  it  in  one  of  two  ways:  In  the  first  place,  the  animal  might  be  placed 
in  a  calorimeter  and  the  heat  given  off  in  twenty-four  hours  be  measured 
directly.  This  method,  which  is  that  of  direct  calorimetry,  is  described  more 
completely  in  the  section  treating  of  Animal  Ileal.  Secondly,  one  might 
feed  the  animal  upon  a  diet  containing  known  quantities  of  proteid,  fats,  and 
carbohydrates,  and  by  collecting  the  total  N  and  C  excreta  determine  how  much 
of  each  of  these  had  been  destroyed  in  the  body.  Knowing  the  combustion 
equivalent  of  each,  the  total  quantity  of  heat  liberated  in  the  body  could  be 
ascertained.  This  latter  method  is  known  as  indirect  calorimetry.  The  two 
methods,  if  applied  simultaneously  to  the  same  animal,  should  give  identical 
results.     It  is  very  interesting  to  know  that  an  experiment  of  this  character 


366 


AX  AMERICA X    TEXT-BOOK    OE  PHYSIOLOGY 


has  been  successfully  performed  by  Rubner;1  his  experiments  were  made  with 
the  greatest  accuracy  and  with  careful  attention  to  all  the  possible  sources  of 
error,  and  it  was  found  that  the  quantities  of  heat  as  determined  by  the  two 
methods  agreed  to  within  less  than  0.5  per  cent.  These  experiments  are  note- 
worthy because  they  furnish  us  with  the  first  successful  experimental  demon- 
stration of  the  accuracy  of  the  general  principles,  stated  above,  upon  which 
the  available  energy  of  foods  is  calculated. 

Dietetics. — The  subject  of  the  proper  nourishment  of  individuals  or  col- 
lections of  individuals — armies,  inmates  of  hospitals,  asylums,  prisons,  etc. — 
is  treated  usually  in  books  upon  hygiene,  to  which  the  reader  is  referred  for 
practical  details.  The  general  principles  of  dieting  have  been  obtained,  how- 
ever, from  experimental  work  upon  the  nutrition  of  animals.  These  principles 
have  been  stated  more  or  less  completely  in  the  foregoing  pages,  but  some 
additional  facts  of  importance  may  be  referred  to  conveniently  at  this  point. 
In  a  healthy  adult  who  has  attained  his  maximum  weight  and  size  the  main 
object  of  a  diet  is  to  furnish  sufficient  nitrogenous  and  non-nitrogenous  food- 
stuffs, together  with  salts  and  water,  to  maintain  the  body  in  equilibrium — 
that  is,  to  prevent  loss  of  proteid  tissue,  fat,  etc.  In  speaking  of  the  nutritive 
value  of  the  food-stuffs  it  was  shown  that  in  carnivora  (dogs)  this  condition 
of  equilibrium  may  be  maintained  upon  proteid  food  alone,  putting  aside  all 
consideration  of  salts  and  water,  or  upon  proteids  and  fats,  or  upon  proteids  and 
carbohydrates,  or  upon  proteids,  fats,  and  carbohydrates.  When  proteids  alone 
are  used,  the  quantity  must  be  increased  far  above  that  necessary  in  the  case  of 
a  mixed  diet,  and  it  is  doubtful  whether,  in  the  case  of  man  or  the  herbivora, 
a  healthy  nutritive  condition  could  be  maintained  long  upon  such  a  diet,  owing 
to  the  largely  increased  demand  upon  the  power  of  the  alimentary  canal  to 
digest  and  absorb  proteids,  to  the  greater  labor  thrown  on  the  kidneys,  etc. 
The  experience  of  mankind,  as  well  as  the  results  of  experimental  investiga- 
tion, shows  that  the  healthy  diet  is  one  composed  of  proteids,  fats,  and  carbo- 
hydrates. The  proportion  in  which  the  fats  and  the  carbohydrates  should  be 
taken — and,  to  a  certain  extent,  this  is  true  also  of  the  proteids — may  be 
varied  within  comparatively  wide  limits,  in  accordance  with  the  law  of  "  iso- 
dynamic  equivalents/'  provided  that  the  total  amount  of  potential  energy  repre- 
sented in  the  food  does  not  fall  below  a  certain  amount,  on  the  average  about 
10,000  calories  per  kilo,  of  body  weight.  This  is  illustrated  by  the  fol- 
lowing "average  diets"  calculated  by  different  physiologists  to  indicate 
the  average  amount  of  food-stuffs  required  by  an  adult  man  under  normal 
conditions  of  Life  : 


Average  Diets. 

Molesehott. 

Ranke. 

Voit. 

Forster. 

Atwater. 

Fats 

Carbohydrates   .... 

130  grams. 
40      " 
550      " 

100  grains. 
100     " 
240     " 

118  grams. 
56      " 
500      " 

131  grams. 
68      " 
494      " 

125  grams. 
125      " 
400      " 

1  ZriUrhnjt  Jiir  Jlmh./ie,  1893,  Bd.  XXX.  S.  73. 


CHEMISTRY  OF  DIGESTION  AND   NUTRITION.  367 

In  Voit's  diet,  which  is  the  one  usually  taken  to  represent  the  daily  Deeds 
of  the  body,  it  will  be  noticed  that  the  ratio  of  the  nitrogenous  to  the  non- 
nitrogenous  food-stuffs  is  about  as  1  :  5,  and  basing  the  estimate  upon  a  man 
weighing  70-75  kilos.,  118  grams  of  proteid  per  day  would  represent  a 
consumption  of  proteid  equal  to  1.3  to  1.7  grams  per  kilo,  of  weight. 
Siven  1  has  recently  attempted  to  show  that  this  proportion  of  proteid  in  food 
is  unnecessarily  high.  In  some  experiments  upon  himself  he  was  able  to 
reduce  his  daily  proteid  food  to  about  0.2  gram  per  kilo,  of  body  weight 
and  still  maintain  his  body  in  N-equilibrium,  provided  the  non-proteid  por- 
tions of  his  diet  were  so  increased  that  the  total  energy  of  his  daily  diet 
remained  unchanged.  Whether  or  not  so  high  an  amount  of  proteid  per  day 
as  118  grams  is  most  beneficial  to  the  body,  under  normal  conditions  of  mod- 
erate labor,  is  perhaps  an  open  question.  It  seems  certain  that  for  short 
periods  at  least  the  average  individual  can  keep  his  body  in  equilibrium  on 
much  smaller  amounts.  It  must  be  remembered,  in  regard  to  these  diets, 
that  the  amounts  of  food-stuffs  given  refer  to  the  dry  material:  118 
grams  of  proteid  do  not  mean  118  grams  of  lean  meat,  for  example,  since 
lean  meat  (flesh)  contains  a  large  proportion  of  water.  Tables  of  analyses  of 
food  (one  of  which  is  given  on  page  278)  enable  us  to  determine  for  each  par- 
ticular article  of  food  the  proportion  of  dry  food-stuffs  contained  in  it,  and  in  how 
great  quantities  it  must  be  taken  to  furnish  the  requisite  amount  of  proteid, 
fats,  or  carbohydrates.  There  is,  however,  still  another  practical  consideration 
that  must  be  taken  into  account  in  estimating  the  nutritive  value  of  articles 
of  food  from  the  analyses  of  their  composition,  and  that  is  the  extent  to  which 
each  food-stuff  in  each  article  of  food  is  capable  of  being  digested  and  absorbed. 
Practical  experience  has  shown  that  proteids  in  certain  articles  of  food  can  be 
digested  and  absorbed  nearly  completely  when  not  fed  in  excess,  while  in  other 
foods  only  a  certain  percentage  of  the  proteid  is  absorbed  under  the  most  favor- 
able conditions.  This  difference  in  usableness  of  the  food-stuffs  in  various 
foods  is  most  marked  in  the  case  of  proteids,  but  it  occurs  also  with  the  fats 
and  the  carbohydrates.  Facts  of  this  kind  cannot  be  determined  by  mere 
analysis  of  the  foods;  they  must  be  obtained  from  actual  feeding  experiments 
upon  man  or  the  lower  animals.  ft  has  usually  been  stated  by  those  who 
have  worked  in  this  field  that  the  proteids  of  meats  are  more  completely  util- 
ized than  those  of  vegetables.  Hut  it  is  possible  that  as  a  generalization  this 
statement  is  too  sweeping,  and  rests  upon  the  erroneous  assumption  that  the 
nitrogen  in  \\'c<^  represents  chiefly  undigested  proteid.  Prausnitz2  and 
others  have  given  reasons  for  believing  that  the  nitrogen  inthefeces  is  derived 
mainly  from  the  intestinal  secretions,  and  that  vegetable  foods  that  do  not 
contain  much  indigestible  material,  such  as  rice  and  bread,  are  practically 
completely  digested  and  absorbed  in  the  intestines,  their  proteids,  therefore, 
being  utilized  as  completely  as  in  the  case  of  meats.      Munk'1  gives  an   inter 

1  Skandinavisehes  Archivfiir  Physiologic,  1899,  Bd.  10,  S.  91. 

1  Zeitsehrifi  fur  Biologie,  L897,  Bd.  35,  S.  835. 

3  Wevl's  Handbuch  der  Hygiene,  L893,  Bd.  iii.  Theil  i.  S.  69. 


368 


AN   AM  ERIC  AX    TEXT-BOOK    OF   PHYSIOLOGY. 


esting  table  showing  how  much  of  certain  familiar  articles  of  food  would  be 
necessary,  if  taken  alone,  to  supply  the  requisite  daily  amount  of  proteid  or 
non-proteid  food ;  his  estimates  are  based  upon  the  percentage  composition 
of  the  fond-,  and  upon  experimental  data  showing  the  extent  of  absorption 
of  the  food-stuffs  in  each  food.  In  this  table  he  supposes  that  the  daily  diet 
should  contain  11<>  grams  of  proteid  =  17.5  grams  of  N,  and  non-proteids 
sufficient  to  contain  270  grains  of  C : 


Milk  .  .  .  . 
Meal  !  lean)  . 
Heu's  eggs 
Wheat  flour  . 
Wheat  bread 
Rye  bread  .  . 
Rice  .  .  .  . 
Corn  .  .  .  . 
Peas  .  .  .  . 
Potatoes     .    . 


For  1K»  grams  proteid 
(17.5  grams  N  I. 


2900 

540 

18 

800 

1650 

1900 

1870 

990 

520 

4500 


grams. 


grams. 


For  270  grams  C. 


3800  grams. 
2000 
37  eggs. 

670  grams. 
1000       " 
1100       " 

750       " 

660 

750 
2550 


As  Munk  points  out,  this  table  shows  that  any  single  food,  if  taken  in  quantities 
sufficient  to  supply  the  nitrogen,  would  give  too  much  or  too  little  C,  and  the  re- 
verse; those  animal  foods  which,  in  certain  amounts,  supply  the  nitrogen  needed 
furnish  only  from  one-quarter  to  two-thirds  of  the  necessary  amount  of  C.  To 
live  for  a  stated  period  upon  a  single  article  of  food — a  diet  sometimes  recom- 
mended to  reduce  obesity — means,  then,  an  insufficient  quantity  of  either  N 
or  C  and  a  consequent  loss  of  body-weight.  Such  a  method  of  dieting  amounts 
practically  to  a  partial  starvation.  In  practical  dieting  we  are  accustomed  to 
get  our  supply  of  proteids,  fats,  and  carbohydrates  from  both  vegetable  and 
animal  foods.  To  illustrate  this  fact  by  an  actual  case,  in  which  the  food  was 
carefully  analyzed,  an  experimenter  (Krummacher)  weighing  67  kilograms 
records  that  he  kept  himself  in  N  equilibrium  upon  a  diet  in  which  the  pro- 
teid was  distributed  as  follows  : 


300  grams  meat 
666. 3  c.c.  milk 
100  grams  rice 
100       "       bread 
500  c.c.  wine 


63.08  grains  proteid 
18.74       " 

7.74       '• 
11.32       "  " 

1.17       " 
102.05       " 


For  a  person  in  health  and  leading  an  active  normal  life,  appetite  and  experi- 
ence seem  to  be  safe  and  sufficient  guides  by  which  to  control  the  diet;  but  iu 
conditions  of  disease,  in  regulating  the  diet  of  children  and  of  collections  of 
individuals,  scientific  dieting,  if  one  may  use  the  phrase,  has  accomplished 
much,  and  will  lie  of  greater  service  as  our  knowledge  of  the  physiology  of 
nutrition  increases. 


VI.  MOVEMENTS  OF  THE  ALIMENTARY  CANAL. 
BLADDER,  AND  URETER. 


Plain  Muscle -tissue. 

The  movements  of  the  alimentary  canal  and  the  organs  concerned  in  mic- 
turition are  effected  for  the  most  part  through  the  agency  of  plain  muscle- 
tissue.  The  general  properties  of  this  tissue  will  be  referred  to  in  the 
section  upon  the  Physiology  of  Muscle  and  Nerve,  but  it  seems  appropriate  in 
this  connection  to  call  attention  to  some  few  points  in  its  general  physiology 
and  histology,  inasmuch  as  the  character  of  the  movements  to  be  described 
depends  so  much  upon  the  fundamental  properties  exhibited  by  this  variety  of 
muscle-tissue.  Plain  muscle  as  it  is  found  in  the  walls  of  the  abdominal  and 
pelvic  viscera  is  composed  of  masses  of  minute  spindle-shaped  cells  whose  size 
is  said  to  vary  from  22  to  560  p.  in  length  and  from  4  to  22  ju  in  width,  the 
average  size,  according  to  Kolliker,  being  100  to  200  fx  in  length  and  4  to  6  u 
in  width.  Each  cell  has  an  elongated  nucleus,  and  its  cytoplasm  shows  a 
longitudinal  fibrillation.  Cross  striation,  such  as  occurs  in  cardiac  and  striped 
muscle,  is  absent.  These  cells  are  united  into  more  or  less  distinct  bundles  or 
fibres,  which  run  in  a  definite  direction  corresponding  to  the  long  axes  of  the 
cells.  The  bundles  of  cells  are  united  to  form  flat  sheets  of  muscle  of  varying 
thicknesses,  which  constitute  part  of  the  walls  of  the  viscera  and  are  distin- 
guished usually  as  longitudinal  and  circular  muscle-coats  according  as  the  cells 
and  bundles  of  cells  have  a  direction  with  or  at  right  angles  to  the  long  axis 
of  the  viscus.  The  constituent  cells  arc  united  to  one  another  by  cement- 
substance,  and  according  to  several  observers1  there  is  a  direct  protoplasmic 
continuity  between  neighboring  cells — an  anatomical  fact  of  interest,  since  it 
makes  possible  the  conduction  of  a  wave  of  contraction  directly  from  one  cell 
to  another.  Plain  muscle-tissue,  in  some  organs  at  least,  e.  g.  the  stomach, 
intestines,  bladder,  and  arteries,  is  under  the  control  of  motor  nerves.  There 
must  be,  therefore,  some  connection  between  the  nerve-fibres  and  the  muscle- 
tissue.  The  nature  of  this  connection  is  not  definitely  established  ;  according 
to  Miller,2  the  nerve-fibres  terminate  eventually  in  line  nerve-fibrils  that  run 
in  the  cement-substance  between  the  cells  and  send  off  small  branches  that 
end  in  a  swelling  applied  directly  to  the  muscle-cell.     Berkley''  finds  a  similar 

1  Sec  I'xilicMiaii  :    A  ii<it<>inisc/i<  r  .1  h-ci'i/it,   I  SKI,   I'.d.   10,  No.  10. 

2  Archiv fur mikro8kopisclii'  Atminmir,  is<i'_>,  |'.<1.  40. 

3  Anatomhcher  Anzeigcr,  1893,  Bd.  8. 

Voi,.  I. —24  369 


370 


AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 


ending  of  the  nerves,  and  in  addition  describes  in  the 
muscularis  mucosae  of  the  intestine  a  large  globular 
end-organ  which  he  considers  as  a  motor  plate. 

Perhaps  the  most  striking  physiological  peculiarity 
of  plain  muscle,  as  compared  with  the  more  familiar 
striated  muscle,  is  the  sluggishness  of  its  contrac- 
tions. Plain  muscle,  like  striated  muscle,  is  inde- 
pendently irritable.  Various  forms  of  artificial 
stimuli,  such  as  electrical  currents,  mechanical, 
chemical,  and  thermal  stimuli,  may  cause  the  tis- 
sue to  contract  when  directly  applied  to  it,  but  the 
contraction  in  all  cases  is  characterized  by  the 
slowness  with  which  it  develops.  There  is  a  long 
latent  period,  a  gradual  shortening  which  may  per- 
sist for  some  time  after  the  stimulus  ceases  to  act, 
and  a  slow  relaxation.  These  features  are  repre- 
sented  in  the  curve  shown  in  Figui'e  68,  which  it  is 
instructive  to  compare  with  the  typical  curve  of  a 
striated  muscle  (Vol.  II.).  The  slowness  of  the  con- 
traction of  plain  muscle  seems  to  depend  upon  the 
absence  of  cross  striation.  Striped  muscle  as  found  in 
various  animals  or  in  different  muscles  of  the  same 
animal — e.  g.  the  pale  and  red  muscles  of  the  rabbit 
— differs  greatly  in  the  rapidity  of  its  contraction, 
and  it  has  been  shown  that  the  more  perfect  the  cross 
striation  the  more  rapid  is  the  contraction.  The 
cross  striation,  in  other  words,  is  the  expression  of  a 
mechanism  or  structure  adapted  to  quick  contractions 
and  relaxations,  and  the  relatively  great  slowness  of 
movement  in  the  plain  muscle  seems  to  result  from 
the  absence  of  this  particular  structure.  It  should  be 
added,  however,  that  plain  muscle  in  different  parts 
of  the  body  exhibits  considerable  variation  in  the 
rapidity  with  which  it  contracts  under  stimulation, 
the  ciliary  muscle  of  the  eyeball,  for  example,  being 
able  to  react  more  rapidly  than  the  muscles  of  the  in- 
testines. The  gentle  prolonged  contraction  of  the  plain 
muscle  is  admirably  adapted  to  its  function  in  the 
intestine  of  moving  the  food-contents  along  the  canal 
with  sufficient  slowness  to  permit  normal  digestion 
and  absorption.  Like  the  striated  muscle,  and  un- 
like the  cardiac  muscle,   plain   muscle  is  capable  of 


I  ;<..  68.— Contraction  of  a  stri]>  of  plain  muscle  from  tin-  stomach  of  a  terrapin.  The  bottom  line 
gives  the  time-record  in  seconds ;  tin-  middle  line  shows  the  time  of  application  of  the  stimulus,  a  tetan- 
izing  current  from  an  induction  coil ;  the  upper  line  is  the  curve  recorded  by  the  contracting  muscle. 


MOVEMENTS    OF    THE  ALIMENTARY    CANAL,    ETC.       371 

giving  submaximal  as  well  as  maximal  contractions;  with  increased  strength 
of  stimulation  the  amount  of  the  shortening  increases  until  a  maximum  is 
reached.  This  fact  may  be  observed  not  only  upon  isolated  strips  of  muscle 
from  the  stomach,  but  may  be  seen  also  in  the  different  degrees  of  contraction 
exhibited  by  the  intestinal  musculature  as  a  whole  when  acted  upon  by  various 
stimuli. 

In  his  researches  upon  the  movements  of  the  ureter  Engelmann  l  showed 
that  a  stimulus  applied  to  the  organ  at  any  point  caused  a  contraction  that. 
starting  from  the  point  stimulated,  might  spread  for  some  distance  in  either 
direction.  Engelmann  interprets  this  to  mean  that  the  contraction  wave  in 
the  case  of  the  ureter  is  propagated  directly  from  cell  to  cell,  and  this  possi- 
bility is  supported  by  the  fact,  before  referred  to,  that  there  is  direct  proto- 
plasmic continuity  between  adjoining  cells.  This  passage  of  a  contraction  wave 
from  cell  to  cell  has,  in  fact,  often  been  quoted  as  a  peculiarity  of  plain 
muscle-tissue.  In  the  case  of  the  ureter  the  fact  seems  to  be  established,  but 
in  the  intestines,  where  there  is  a  rich  intrinsic  supply  of  nerve-ganglia,  it 
is  not  possible  to  demonstrate  clearly  that  the  same  property  is  exhibited. 
The  wave  of  contraction  in  the  intestine  following  artificial  stimulation  is, 
according  to  most  observers,  usually  localized  at  the  point  stimulated  or  is 
propagated  in  only  one  direction,  and  these  facts  are  difficult  to  reconcile 
with  the  hypothesis  that  each  cell  may  transmit  its  condition  of  activity 
directly  to  neighboring  cells.  Upon  the  plain  muscle  of  the  ureter  Engel- 
mann was  able  to  show  also  an  interesting  resemblance  to  cardiac  muscle, 
in  the  fact  that  each  contraction  is  followed  by  a  temporary  diminution  in 
irritability  and  conductivity  ;  but  this  important  property,  which  in  the  case  of 
the  heart  has  been  so  useful  in  explaining  the  rhythmic  nature  of  its  contrac- 
tions, has  not  been  demonstrated  for  all  varieties  of  plain  muscle  occurring  in 
the  body. 

A  general  property  of  plain  muscle  that  is  of  great  significance  in  explain- 
ing the  functional  activity  of  this  tissue  is  exhibited  in  the  phenomenon  of 
"tone."  By  tone  or  tonic  activity  as  applied  to  muscle-tissue  is  meant  a  con- 
dition of  continuous  contraction  or  shortening  that  persists  for  long  periods 
and  may  be  slowly  increased  or  decreased  by  various  conditions  affecting  the 
muscle.  Both  striated  and  cardiac  muscle  exhibit  tone,  and  in  the  latter  at 
least  the  condition  may  be  independent  of  any  inflow  of  nerve-impulses  from 
the  extrinsic  nerves.  Plain  muscle  exhibits  the  property  in  a  marked  degree. 
The  muscular  coats  of  the  alimentary  canal,  the  blood-vessels,  the  bladder, 
etc.,  are  usually  found  under  normal  circumstances  in  a  condition  of  tone 
that  varies  from  time  to  time  and  differs  from  an  ordinary  visiUe  contraction 
in  the  slowness  with  which  it  develops  and  in  its  persistence  for  long  periods. 
Such  conditions  as  the  reaction  of  the  blood,  for  example,  are  known  to  alter 
greatly  the  tone  of  the  blood-vessels,  a  less  alkaline  reaction  than  normal 
causing  relaxation,  while  an  increase  in  alkalinity  favor-  the  development  of 
tone.  Tone  may  also  be  increased  or  diminished  by  the  action  of  motor  or 
1  I'jliii/ir'x  Archivfur  die  gesammte  Physiologie,  1869,  Bd.  -',  S  243. 


372  AN  AMERICAN   TEXT-BOOK   OF    PHYSIOLOGY. 

inhibitory  nerve-fibres,  but  the  precise  relationship  between  the  changes 
underlying  the  development  of  tone  and  those  leading  to  the  formation  of  an 
ordinary  contraction  has  not  been  satisfactorily  determined. 

The  mode  of  contraction  of  the  plain  muscle  in  the  walls  of  some  of  the 
viscera,  especially  the  intestine  and  meter,  is  so  characteristic  as  to  be  given 
the  special  name  of  peristalsis.  I>y  peristalsis,  or  vermicular  contraction  as  it 
is  sometimes  called,  is  meant  a  contraction  which,  beginning  at  any  point  in 
the  wall  of  a  tubular  viscus,  is  propagated  along  the  length  of  the  tube  in  the 
form  of  a  wave,  each  part  of  the  tube  as  the  wave  reaches  it  passing  slowly 
into  contraction  until  the  maximum  is  reached,  and  then  gradually  relaxing. 
In  viscera  like  the  intestine,  in  which  two  muscular  coats  are  present,  the 
longitudinal  and  the  circular,  the  peristalsis  may  involve  both  layers,  either 
simultaneously  or  successively,  but  the  striking  feature  observed  when  watching 
the  movement  is  the  contraction  of  the  circular  coat.  The  contraction  of  this 
coat  causes  a  visible  constriction  of  the  tube  that  may  be  followed  by  the  eye 
as  it  passes  onward. 

Mastication. 

Mastication  is  an  entirely  voluntary  act.  The  articulation  of  the  mandi- 
bles with  the  skull  permits  a  variety  of  movements  ;  the  jaw  may  be  raised 
and  lowered,  may  be  projected  and  retracted,  or  may  be  moved  from  side  to 
side,  or  various  combinations  of  these  different  directions  of  movement  may  be 
effected.  The  muscles  concerned  in  these  movements  and  their  innervation  are 
described  as  follows:  The  masseter,  temporal  and  internal  pterygoids  raise  the 
jaw  ;  these  muscles  are  innervated  through  the  inferior  maxillary  division  of 
the  trigeminal.  The  jaw  is  depressed  mainly  by  the  action  of  the  digastric 
muscle,  assisted  in  some  cases  by  the  mylo-hyoid  and  the  geniohyoid.  The 
two  former  receive  motor-fibres  from  the  inferior  maxillary  division  of  the 
fifth  cranial,  the  last  from  a  branch  of  the  hypoglossal.  The  lateral  movements 
of  the  jaws  are  produced  by  the  external  pterygoids,  when  acting  separately. 
Simultaneous  contraction  of  these  muscles  on  both  sides  causes  projection  of 
the  lower  jaw.  In  this  latter  case  forcible  retraction  of  the  jaw  is  produced  by 
the  contraction  of  a  part  of  the  temporal  muscle.  The  external  pterygoids 
also  receive  their  motor  fibres  from  the  fifth  cranial  nerve,  through  its  inferior 
maxillary  division.  The  grinding  movements  commonly  used  in  masticating 
the  food  between  the  molar  teeth  are  produced  by  a  combination  of  the  action 
of  the  external  pterygoids,  the  elevators,  and  perhaps  the  depressors.  At  the 
same  time  the  movements  <<i'  the  tongue  and  of  the  muscles  of  the  cheeks  and 
iips  serve  to  keep  the  food  properly  placed  for  the  action  of  the  teeth,  and  to 
gather  it  into  position  for  the  act  of  swallowing. 

Deglutition. 

The  act  of  swallowing  is  a  complicated  reflex  movement  which  may  be 
initiated  voluntarily,  but   i-   for  the  most  part  completed  quite  independently 


MOVEMENTS    OE    THE   ALIMENTARY    CANAL,    ETC.        373 

of  the  will.  The  classical  description  of  the  act  given  by  Magendie  divides  it 
into  three  stages,  corresponding  to  the  three  anatomical  regions,  the  mouth, 
pharynx  and  oesophagus,  through  which  the  swallowed  morsel  passes  on  its 
way  to  the  stomach.  The  first  stage  consists  in  the  passage  of  the  bolus  of 
food  through  the  isthmus  of  the  fauces — that  is,  the  opening  lying  between  the 
ridges  formed  by  the  palato-glossi  muscles,  the  so-called  anterior  pillars  of  the 
fauces.  This  part  of  the  act  is  usually  ascribed  to  the  movements  of  the  tongue 
itself.  The  bolus  of  food  lying  upon  its  upper  surface  is  forced  backward  by 
the  elevation  of  the  tongue  against  the  soft  palate  from  the  tip  toward  the  base. 
This  portion  of  the  movement  may  be  regarded  as  voluntary,  to  the  extent  at 
least  of  manipulating  the  food  into  its  proper  position  on  the  dorsum  of  the 
tongue,  although  it  is  open  to  doubt  whether  the  entire  movement  is  usually 
effected  by  a  voluntary  act.  Under  normal  conditions  the  presence  of  moist 
food  upon  the  tongue  seems  essential  to  the  complete  execution  of  the  act ; 
and  an  attempt  to  make  the  movement  with  very  dry  material  upon  the  tongue 
is  either  not  successful  or  is  performed  with  difficulty.  The  second  act  com- 
prises the  passage  of  the  bolus  from  the  isthmus  of  the  fauces  to  the  (esophagus 
— that  is,  its  transit  through  the  pharynx.  The  pharynx  being  a  common 
passage  for  the  air  and  the  food,  it  is  important  that  this  part  of  the  act  should 
be  consummated  quickly.  According  to  the  usual  description  the  motor  power 
driving  the  bolus  downward  through  the  pharynx  is  derived  from  the  contrac- 
tion of  the  pharyngeal  muscles,  particularly  the  constrictors,  which  contract  from 
above  downward  and  drive  the  food  into  the  oesophagus.  Simultaneously, 
however,  a  number  of  other  muscles  are  brought  into  action,  the  general  effect 
of  which  is  to  shut  off  the  nasal  and  laryngeal  openings  and  thus  prevent  the 
entrance  of  food  into  the  corresponding  cavities.  The  whole  reflex  is  therefore 
an  excellent  example  of  a  finely  co-ordinated  movement. 

The  following  events  are  described  :  The  mouth  cavity  is  shut  off  by 
the  position  of  the  tongue  against  the  palate  and  by  the  contraction  of  the 
muscles  of  the  anterior  pillars  of  the  fauces.  The  opening  into  the  nasd  cavity 
is  closed  by  the  elevation  of  the  soft  palate  (action  of  the  levator  palati  and 
tensor  palati  muscles)  and  the  contraction  of  the  posterior  pillars  of  the  fauces 
(palato-pharyngei  muscles)  and  the  elevation  of  the  uvula  (azygos  uvulae  mus- 
cle). The  soft  palate,  uvula,  and  posterior  pillars  thus  form  a  sloping  surface 
shutting  oil'  the  nasal  chamber  and  facilitating  the  passage  of  the  food  backward 
into  the  pharynx  where  the  constrictor  muscles  may  act  upon  it.  The  respira- 
tory opening  into  the  larynx  is  closed  by  the  adduction  of  the  vocal  cords  (lat- 
eral crico-arytenoids  and  constrictors  of  the  glottis)  and  by  the  elevation  of  the 
entire  larynx  and  a  depression,  in  pari  mechanical,  of  the  epiglottis  over  the 
larynx  (action  of  the  thyro-hyoids,  digastrics,  genio-hyoids,  and  mylo-hyoids 
and  the  muscles  in  the  aryteno-epiglottidean  folds).  The  movements  of  the 
epiglottis  during  this  stage  of  swallowing  have  been  much  discussed.  The 
usual  view  is  that  it  is  pressed  down  upon  the  laryngeal  orifice  like  the  lid  of 
a  box  and  thus  effectually  protects  the  respiratory  passage.  Ii  has  been  shown, 
however,  that   removal  of  the  epiglottis  does  not    prevent  normal  swallowing, 


374  AN   AMERICAN    TEXT- HOOK   OF  PHYSIOLOGY. 

and  Stuart  and  Mc<  iormick  '  have  reported  the  case  of  a  man  in  whom  part 
dt'  the  pharynx  had  been  permanently  removed  by  surgical  operation  and  in 
whom  the  epiglottis  could  he  seen  during  the  act  of  swallowing.  In  this 
individual,  according  to  their  observations,  the  epiglottis  was  not  folded  back 
during  swallowing,  but  remained  erect.  hater  observations  by  Kanthack  and 
Anderson,2  made  partly  upon  themselves  and  partly  upon  the  lower  animals, 
(end,  on  the  contrary,  to  support  the  older  view.  They  state  that  in  norma1 
ndividuals  the  movement  of  the  epiglottis  backward  during  swallowing  m;i\ 
be  felt  by  simply  passing  the  linger  back  into  the  pharynx  until  it  conies  into 
contact  with  the  epiglottis.  At  the  beginning  of  the  movement  there  is  also  a 
contraction  of  the  longitudinal  muscles  of  the  pharynx  which  tends  to  pull  the 
pharyngeal  walls  toward  the  bolus  of  food  while,  as  has  been  said,  the  nearly 
simultaneous  contraction  of  the  constrictors  presses  upon  the  food  and  forces 
it  downward.  The  food  is  thus  brought  quickly  into  the  opening  of  the 
oesophagus  and  the  third  stage  commences. 

The  transit  of  the  food  through  the  oesophagus  is  effected  by  the  action 
of  its  intrinsic  musculature.  The  muscular  coat  is  arranged  in  two  layers,  an 
external  longitudinal  and  an  internal  circular.  These  are  composed  of  plain 
muscle-tissue  in  the  lower  third  or  two-thirds  of  the  oesophagus,  but  in  most 
mammals  tiic  upper  third  or  more  contains  striated  muscular  tissue.  The 
chief  factor  in  the  transportation  of  the  bolus  through  the  oesophagus  has 
been  supposed  to  consist  in  the  contraction  of  the  circular  muscle.  This  con- 
traction begins  at  the  pharyngeal  opening  of  the  oesophagus  and  passes  down- 
ward in  the  form  of  a  wave,  peristaltic  contraction,  which  moves  rapidly  in  the 
upper  segment  where  the  musculature  is  striated,  and  more  slowly  in  the  lower 
segments  in  accordance  with  the  physiological  characteristics  of  plain  muscle. 
The  result  of  this  movement  would  naturally  be  to  force  the  food  onward  to 
the  stomach.  The  longitudinal  muscles  of  the  oesophagus  are  without  doubt 
brought  into  action  at  the  same  time,  but  in  this  as  in  other  cases  of  peristalsis 
in  tubular  viscera  it  is  not  perfectly  clear  how  they  co-operate  in  producing 
the  onward  movement.  It  may  be  that  their  contraction  slightly  precedes 
that  of  the  circular  muscle,  and  thus  tends  to  dilate  the  tube  and  to  bring  it 
forward  over  the  bolus.  At  the  opening  of  the  oesophagus  into  the  stomach, 
the  cardiac  orifice,  the  circular  fibres  of  the  oesophagus  function  as  a  sphincter 
which  is  normally  in  a  condition  of  tone,  particularly  when  the  stomach  con- 
tains food,  and  thus  shuts  off  the  cavity  of  the  stomach  from  the  oesophagus.  - 
In  swallowing,  however,  the  advancing  peristaltic  wave  has  sufficient  force  to 
overcome  the  tonicity  of  the  sphincter,  or  possibly  there  is  at  this  moment  a 
reflex  inhibition  of  the  sphincter.  In  either  case  the  result  is  that  the  food 
is  forced  through  the  narrow  opening  into  the  stomach  with  sufficient  energy 
to  give  rise  to  a  sound  that  may  be  heard  by  auscultation  over  this  region.3 
According  to  measurements  by  Kronecker  and  Meltzer  the  entrance  of  the 

1  Journal  of  Anatomy  mul  Physiology,  1892. 

7  Journal  of  Physiology,  Is'.1.".,  vol.  xiv.  p.  154. 

3  See  Meltzer:   CentroJblatt  fur  die  med.  Wissenschaften,  1881,  No.  1. 


MOVEMENTS    OF    THE  ALIMENTARY  CANAL,    ETC.       375 

food  into  the  stomach  occurs  in  mail  about  six  seconds  alter  the  beginning  of 
the  act  of  swallowing. 

Kronecker-Meltzer  Theory  of  Deglutition. — The  usual  view  of  the 
mechanism  of  -wallowing  has  been  seriously  modified  by  Kronecker  and 
Meltzer.1  The  experiments  of  these  observers  seem  to  be  so  conclusive  that 
we  must  believe  that  in  the  main  their  explanation  of  the  process  is  correct. 
According  to  their  view  the  chief  factor  in  forcing  soft  or  liquid  food  through 
the  pharynx  and  oesophagus  is  the  sharp  and  strong  contraction  of  the  mylo- 
hyoid muscles.  The  bolus  of  food  lies  upon  the  dorsum  of  the  tongue  and 
by  the  pressure  of  the  tip  of  the  tongue  against  the  palate  it  is  shut  off  from 
the  front  part  of  the  mouth-cavity.  The  mylo-hyoids  now  contract,  and  the 
bolus  of  food  is  put  under  high  pressure  and  is  shot  in  the  direction  of  least 
resistance — namely,  through  the  pharynx  and  oesophagus.  This  effect  is  aided 
by  the  simultaneous  contractions  of  the  hyoglossi  muscles,  which  tend  to  still 
further  increase  the  pressure  upon  the  food  by  moving  the  tongue  backward 
and  downward.  This  same  movement  of  the  tongue  suffices  also  to  depress 
the  epiglottis  over  the  larynx,  and  thus  protect  the  respiratory  opening.  Bv 
means  of  small  rubber  bags  connected  with  recording  tambours,  which  were 
placed  in  the  pharynx  and  at  different  levels  in  the  oesophagus,  they  were  able 
to  demonstrate  the  rapid  spirting  of  the  food  through  the  whole  length  of 
pharynx  and  into  the  oesophagus,  the  time  elapsing  between  the  beginning  of 
the  swallowing  movement  and  the  arrival  of  the  food  at  the  lower  end  of  the 
oesophagus  being  not  more  than  0.1  second.  The  contraction  of  the  con- 
strictors of  the  pharynx  and  the  peristaltic  wave  along  the  oesophagus,  ac- 
cording to  this  view,  normally  follow  after  the  food  has  been  swallowed,  and 
may  be  regarded  as  a  movement  in  reserve  which  is  useful  in  removing 
adherent  fragments  along  the  deglutition  passage,  or  possibly,  in  cases  of  the 
failure  of  the  first  swallowing  act  from  any  cause — as  may  result,  for  instance, 
in  swallowing  food  too  dry  or  too  solid — serves  actually  to  push  the  bolus 
downward,  although  at  a  much  slower  rate.  From  auscultation  of  the  deglu- 
tition sound  which  ensues  when  the  food  enters  the  stomach  through  the 
cardia.  Kronecker  and  Meltzer  believe  that  usually  the  swallowed  food  alter 
reaching  the  lower  portion  of  the  oesophagus  does  not  enter  the  stomach 
until  the  subsequent  peristaltic  wave  of  the  (esophagus,  which  reaches  the 
same  point  in  about  six  seconds  after  the  beginning  of  the  act  of  swallowing, 
forces  it  through.  According  to  Cannon  and  Moser,2  the  rapid  projection  of 
food  into  the  deeper  part  of  the  (esophagus  occurs  only  with  liquids.  When 
the  food  is  solid  or  semisolid  peristalsis  is  required  to  move  the  bolus  through 
the  oesophagus.  Kronecker  and  Meltzer  were  able  to  determine  hv  their 
method  of  recording  thai  the  human  oesophagus  contracts  apparently  in  three 
successive  segments.  The  first  of  these  comprises  about  six  centimeters  in 
the  neck  region,  and  its  contraction  begins  about  1  or   1.2  seconds  after  the 

1  Archiv  f ii r  I'litfslnlof/ir,  1883,  Suppl.  I'd.,  S.  328 ;   also  Journal  of  Experimental  Medicine, 
1897,  vol.  ii.  p.  453. 

2  American  Journal  of  Physiology,  1898,  vol.  i.  p.  435. 


376  AN   AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

beginning  of  swallowing  and  is  comparatively  short,  lasting-  2  seconds,  corre- 
sponding to  the  striated  character  of  the  muscle.  The  second  segment  covers 
about  ten  centimeters  of  the  upper  thoracic  portion  of  the  (esophagus;  its  con- 
traction begins  about  1.8  seconds  after  the  beginning  of  the  contraction  of  the 
first  segment,  and  is  longer,  lasting  (J  to  7  seconds.  The  third  segment  includes 
the  remainder  of  the  oesophagus  :  its  contraction  begins  about  3  seconds  after 
the  contraction  of  the  second  segment,  and  lasts  a  much  longer  time,  ahout  9— 10 
seconds.  These  figures  apply,  of  course,  to  a  single  act  of  swallowing.  It 
will  be  seen  that  according  to  these  authors  the  swallowing  reflex  consists 
essentially  in  the  successive  contractions  of  five  muscular  segments  or  hands — 
namely,  the  mylo-hyoids,  the  constrictors  of  the  pharynx,  and  the  three  seg- 
ment.- of  the  oesophagus  described.  The  time  elapsing  between  the  contractions 
of  these  successive  parts  was  determined  as  follow.-  : 

From  the  beginning  of  the  contraction  of  the  mylo-hyoids  to  that  of  the 

constrictors  of  the  pharynx , 0.3  second. 

From   the  beginning  of  the    contraction  of  the  constrictors  to   that  of 

the  first  esophageal  segment 0.9      " 

Between  the  first  and  second  oesophageal  segments 1.8  seconds. 

"  "    second  and  third         "  "  3.0       " 

The  total  time  before  the  wave  of  contraction  reaches  the  stomach  would 
be  therefore,  as  has  been  stated,  about  six  seconds.  When  a  second  act  of 
-wallowing  is  made  within  six  seconds  of  the  first  swallow  it  causes  an  inhibi- 
tion, apparently  by  a  reflex  effect  upon  the  deglutition  centre,  of  the  part  of 
the  tract  which  has  not  yet  entered  into  contraction,  so  that  the  peristaltic 
wave  does  not  reach  the  lower  end  of  the  oesophagus  until  six  seconds  after 
the  second  act  of  swallowing. 

Nervous  Control  of  Deglutition. — The  entire  act  of  swallowing,  as  has 
been  said  before,  is  essentially  a  reflex  act.  Even  the  comparatively  simple 
wave  of  contraction  that  sweeps  over  the  (esophagus  is  apparently  due  to  a 
reflex  nervous  stimulation,  and  is  not  a  simple  conduction  of  contraction  from 
one  portion  of  the  tube  to  another.  This  fact  Mas  demonstrated  by  the 
experiment-  of  Mosso,1  who  found  that  after  removal  of  an  entire  segment 
from  the  oesophagus  the  peristaltic  wave  passed  to  the  portion  of  the  oesoph- 
agi- left  on  the  stomach  side  in  spite  of  the  anatomical  break.  The  same 
experiment  was  performed  successfully  on  rabbits  by  Kronecker  and  Meltzer. 
Observation  of  the  stomach  end  of  the  oesophagus  in  this  animal  showed  tliat 
it  went  into  contraction  two  seconds  after  the  beginning  of  a  swallowing  act 
whether  the  (esophagus  was  intact  or  ligated  or  completely  divided  by  a  trans- 
verse incision.  The  afferent  nerves  concerned  in  this  reflex  are  the  sensory 
fibres  to  the  mucous  membrane  of  the  pharynx  and  (esophagus,  including 
branches  of  the  glossopharyngeal,  trigeminal,  vagus,  and  superior  laryngeal 
division  of  the  vagus.  Artificial  stimulation  of  this  last  nerve  in  the  lower 
animal-  is  known  t.»  produce  -wallowing  movements.  Wassilieff2  records  that 
in  rabbit-  he  was  able  to  produce  the  -wallowing  reflex  by  artificial  stimula- 
tion of  the  mucous  membrane  of  the  soft   palate  over  a  definite  area.     The 

1  Mol  schotea  UnU  rsuchungm,  L876,  lid.  xi.        •  X,  Uschrifi  fur  Biologie,  1S88,  Ed.  24,  S.  29. 


MOVEMENTS    OF    THE   ALIMENTARY   CANAL,    ETC.        377 

sensory  fibres  to  this  area  arise  from  the  trigeminal  nerve.  The  same  observer, 
in  experiments  upon  himself,  was  unable  to  locate  any  particular  area  of  the 
mucous  membrane  of  the  mouth  that  seemed  to  be  especially  connected  with 
the  swallowing  reflex.  The  physiological  centre  of  the  reflex  is  supposed  to  lie 
quite  far  forward  in  the  medulla,  but  its  anatomical  boundaries  have  not  been 
satisfactorily  defined.  It  seems  probable  that  in  this  as  in  other  cases  the 
physiological  centre  is  not  a  circumscribed  collection  of  nerve-cells,  but  com- 
prises certain  portions,  more  or  less  scattered,  of  the  nuclei  of  origin  of  the 
efferent  fibres  to  the  muscles  of  deglutition.  These  muscles  are  innervated  by 
fibres  from  the  hypoglossal,  facial,  trigeminal,  glossopharyngeal,  and  vagus. 
The  latter  nerve  supplies  through  some  of  its  branches  the  entire  oesophagus 
as  well  as  some  of  the  pharyngeal  muscles,  the  muscles  closing  the  glottis,  and 
the  aryteno-epiglottideau,  which  is  supposed  to  aid  in  depressing  the  epiglottis. 

Movements  of  the  Stomach. 

The  musculature  of  the  stomach  is  usually  divided  into  three  layers,  a  lon- 
gitudinal, an  oblique,  and  a  circular  coat.  The  longitudinal  coat  is  continuous 
at  the  cardia  with  the  longitudinal  fibres  of  the  oesophagus  ;  it  spreads  out  from 
this  point  along  the  length  of  the  stomach,  forming  a  layer  of  varying  thick- 
ness ;  along  the  curvatures  the  layer  is  stronger  than  on  the  front  and  posterior 
surfaces,  while  at  the  pyloric  end  it  increases  considerably  in  thickness,  and 
passes  over  the  pylorus  to  be  continued  directly  into  the  longitudinal  coat  of 
the  duodenum.  The  layer  of  oblique  fibres  is  quite  incomplete ;  it  seems  to  be 
continuous  with  the  circular  fibres  of  the  oesophagus  and  spreads  out  from  the 
cardia  for  a  certain  distance  over  the  front  and  posterior  surfaces  of  the  fundus 
of  the  stomach,  but  toward  the  pyloric  end  disappears,  seeming  to  pass  into 
the  circular  fibres.  The  circular  coat,  which  is  placed  between  the  two  pre- 
ceding layers,  is  the  thickest  and  most  important  part  of  the  musculature  of 
the  stomach.  At  the  extreme  left  end  of  the  fundus  the  circular  bands  are 
thin  and  somewhat  loosely  placed,  but  toward  the  pyloric  end  they  increase 
much  in  thickness,  forming  a  strong  muscular  mass,  which,  as  we  shall  see, 
plays  the  most  important  part  in  the  movements  of  the  stomach.  At  the  pylo- 
rus itself  a  special  development  of  this  layer  functions  as  a  sphincter  pylori, 
which  with  the  aid  of  a  circular  fold  of  the  mucous  membrane  makes  it 
possible  to  shut  off  the  duodenum  completely  or  partially  from  the  cavity 
of  the  stomach.  The  portion  of  the  stomach  near  the  pylorus  is  fre- 
quently designated  simply  as  the  "pyloric  part,"  but  owing  to  its  distinct 
structure  and  functions  the  more  specific  name  of  "antrum  pylori"  seema 
preferable.  The  line  of  separation  between  flic  antrum  pylori  and  the  body 
or  fundus  of  the  stomach  is  made  by  a  special  thickening  of  the  circular  fibres 
which  forms  a  structure  known  as  the  "transverse  band"  by  the  older 
writers,1  and  described  more  recently2  as  the  "sphincter  antri  pylorici/' 
This  so-called  sphincter  lies  at  a  distance  of  seven  to  ten  centimeters  from  the 

1  See  Beaumont:   Physiology  <;/"  Digestion,  2d  ed.,  1  s  17,  p.  104. 

2  Ilofmeister  and  Schiitz  :  Archiv  fur  eocper.  Pathologie  and  Pharmakologie,  1886,  Bd.  xx. 


378  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

pylorus.  Between  it  and  the  pylorus  is  the  "antrum  pylori,"  of  which  the 
distinguishing  features  are  the  comparative  smoothness  and  paleness  of  the 
mucous  membrane,  the  presence  of  the  pyloric  as  distinguished  from  the  fuudic 
glands,  and  the  existence  of  a  relatively  very  strong  musculature. 

The  movements  of  the  stomach  during  digestion  have  been  the  subject  of 
much  study  and  experimentation,  both  in  man  and  the  lower  animals,  but  it 
cannot  be  said  that  the  mechanism  of  the  movements  is  as  yet  completely 
understood.  The  fundamental  fact  to  be  borne  in  mind  is  that  during  a 
period  of  several  hours  after  ordinary  food  is  received  into  the  stomach  the 
musculature  of  this  organ  contracts  in  such  a  way  as  to  keep  the  contents  in 
movement,  while  from  time  to  time  the  thinner  portions  of  the  semi-digested 
food  are  sent  through  the  pylorus  into  the  duodenum.  There  is  a  certain 
orderliness  in  the  movement,  and  especially  in  the  separation  and  ejection  of 
the  more  liquid  from  the  solid  parts,  which  indicates  that  the  whole  act  is 
well  co-ordinated  to  a  definite  end.  The  older  physiologists  spoke  of  a  selec- 
tive power  of  the  pylorus  in  reference  to  the  recurring  acts  of  ejection  of  the 
more  liquid  portions  into  the  intestine,  but  a  phrase  of  this  kind,  as  applied  to 
a  muscular  apparatus,  is  permissible  only  as  a  figure  of  speech,  and  throws  no 
light  whatever  upon  the  nature  of  the  process.  It  has  been  the  object  of 
recent  investigations  to  discover  the  mechanical  factors  involved  in  these  acts 
and  their  relations  to  the  musculature  known  to  be  present.  It  has  been  shown 
satisfactorily  that  the  movements  of  the  stomach  are  not  dependent  upon  its 
connection  with  the  central  nervous  system.  The  stomach  receives  a  rich  sup- 
ply of  extrinsic  nerve-fibres,  some  of  which  are  distributed  to  its  muscles  and 
serve  to  regulate  its  movements,  as  will  be  described  later;  but  when  these 
extrinsic  nerves  are  all  severed,  and  indeed  when  the  stomach  is  completely 
removed  from  the  body,  its  movements  may  still  continue  in  apparently  a 
normal  way  so  long  as  proper  conditions  of  moisture  and  temperature  are 
maintained.  We  must  believe,  therefore,  that  the  stomach  is  an  automatic 
organ,  using  the  word  automatic  in  a  limited  sense  to  imply  essential  independ- 
ence of  the  central  nervous  system.  The  normal  stomach  at  rest  is  usually 
quiet,  and  the  stimulus  to  its  movements  comes  from  the  presence  of  the  solid 
or  liquid  material  received  into  it  from  the  cesophagns.  Upon  the  reception 
of  this  material  the  movements  begin,  at  first  feebly  but  gradually  increasing  in 
extent,  and  continue  until  most  or  all  of  the  material  has  been  sent  into  the 
duodenum,  the  length  of  time  required  depending  upon  the  nature  and  amount 
of  the  food.  The  exact  character  of  the  movements  has  been  variously  de- 
scribed by  different  observers.  Upon  man  they  were  carefully  studied  by 
Beaumont1  in  his  famous  observations  upon  Alexis  St.  Martin  (see  p.  2<S<S  , 
ami  many  points  in  his  description  have  of  late  years  been  confirmed  by  ex- 
periments upon  dogs  and  cats,- whose  stomachs  resemble  that  of  man.     These 

1  The  Physiology  of  Digestion,  1883. 

1  J  lofmei^ter  und  Schiitz:  Archiv  fur  exper.  Pathologie  und  Pharmakologie,  1886,  Bd  xx. ; 
Moritz:  Zeitschrifl  fur  Biologie,  189-"),  Bd.  xxxii. ;  Rossbach :  Deutsches  Archiv  fiir  klinische 
Medicin,  1890,  Bd.  xlvi. ;  Cannon:  American  Journal  of  Physiology,  1898,  i.  359. 


MOVEMENTS    OF    THE  ALIMENTARY   CANAL,    ETC.       379 

observations  all  tend  to  show  that  the  main  movements  of  the  stomach  are 
effected  by  the  musculature  of  the  antrum  pylori,  whose  contraction  is  not  only 
the  chief  factor  in  ejecting  the  material  into  the  duodenum,  but  also  aids  in 
keeping  the  contents  of  the  stomach  in  motion.  The  extent  to  which  contrac- 
tions occur  in  the  fundic  end  of  the  stomach  does  not  seem  to  be  so  clearly  de- 
termined. According  to  some  observers  rhythmic  movements  are  absent  in  the 
fundus  to  the  left  of  about  the  middle  of  the  stomach,  this  portion  simply  re- 
maining in  a  condition  of  tone ;  according  to  others  the  contractions  begin  near 
the  oesophageal  opening  and  pass  thence  toward  the  pylorus.  According  to 
Cannon's  observations  on  the  cat,  the  fundic  end  toward  the  close  of  digestion 
enters  into  a  gradually  increasing  condition  of  tone  that  squeezes  its  contents 
forward  into  the  pre-antral  region. 

According  to  Hofmeister  and  Sehiitz,  a  normal  movement  begins  near  the 
cardia  by  a  flattening  or  constriction  which  is  feeble  and  is  apparent  only  on 
the  side  of  the  great  curvature.  This  constriction  is  due  to  a  contraction  of 
the  circular  muscle-fibres,  and  the  wave  thus  started  passes  toward  the  pylorus, 
increasing  in  strength  as  it  goes,  while  the  parts  behind  previously  in  contrac- 
tion slowly  relax.  This  peristaltic  wave  comes  to  a  stop  a  short  distance  in 
front  of  the  antrum  pylori  by  a  constriction  involving  the  whole  circumference 
of  the  stomach,  to  which  these  authors  gave  the  name  of  the  "pre-antral" 
constriction ;  it  seems  to  mark  the  climax  of  the  peristaltic  movement.  The 
obvious  effect  of  this  movement  so  far  would  be  to  push  forward  some  of  the 
contents  of  the  fundus  into  the  antrum.  Immediately  upon  the  formation  of 
this  constriction  the  strong  "  sphincter  antri  pyloric!  "  or  transverse  band  which 
marks  the  beginning  of  the  antrum,  contracts  strongly — so  strongly,  in  fact,  in 
what  may  be  considered  normal  movements,  as  to  cut  off  entirely  the  antrum 
pylori  from  the  fundus.  Following  upon  this  the  musculature  of  the  antrum 
contracts  as  a  whole,  squeezing  upon  its  contents  and  sending  them  through  the 
narrow  opening  of  the  pylorus  into  the  duodenum.  If,  however,  the  contents 
of  the  antrum  are  not  entirely  liquid,  but  contain  some  solid  particles  too  huge 
to  escape  through  the  narrow  pylorus,  their  presence  seems  to  stimulate  an 
"  antiperistaltic"  wave  in  the  musculature  of  the  antrum  pylori — that  is,  a  mus- 
cular wave  running  in  the  reverse  direction  to  that  of  a  normal  one,  from  right 
to  left,  the  effect  of  which  is  to  throw  back  these  solid  particles  into  the  fundus, 
which  is  now  in  communication  with  the  antrum,  the  sphincter  antri  pyloric! 
having  relaxed.  This  reversed  wave  in  the  antrum  seems  to  have  been  observed 
repeatedly  by  Beaumont  upon  the  human  stomach,  as  well  as  by  Hofmeister 
and  Sehiitz  upon  the  dog's  stomach,  and  enables  us  to  understand  how  solid 
particles  thrown  against  the  pylorus  arc  again  forced  back  into  the  fundus  to 
undergo  further  digestive  and  mechanical  action.  According  to  other 
observers,  the  contractions  of  the  sphincter  antri  pyloric)  arc  not  strong 
enough  to  cut  off  completely  the  antrum,  and  the  antrum  does  not  contract  a- 
a  whole.  The  peristaltic  waves  simply  run  over  this  portion  with  increasing 
strength  forcing  the  food  against  the  pylorus.  These  movements,  a-  a 
whole,  from   fundus   to   pylorus   occur   with   a   certain    rapidity  which   varies 


380  AN    AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

with  the  nature  and  amount  of  the  contents  of  the  stomach  and  the  period  of 
digestion.  In  Beaumont's  observations  the  movements  of  the  pylorus  are 
recorded  as  following  each  other  at  intervals  of  two  to  three  minutes,  while 
upon  cats,  according  to  Cannon's  observations,  the  peristaltic  waves  in  the 
pyloric  part   follow  at  regular  intervals  of  about  ten  seconds. 

It  will  he  seen  that  according  to  this  description  the  movements  occur  in 
two  phases:  first,  the  feeble  peristaltic  movement  running  over  the  fundus 
chiefly  .m  the  side  of  the  great  curvat ure  and  resulting  in  pushing  some  of 
the  fundic  contents  into  the  antrum  ;  second,  the  stronger  contractions  of  the 
antrum,  the  effect  of  which  is  to  squeeze  some  of  the  contents  into  the  duo- 
denum. Whether  or  not  the  musculature  of  the  antrum  shows  only  stronger 
peristaltic  waves,  or  contracts  as  a  whole,  with  some  suddenness  after  the 
manner  of  a  systole,  as  described  by  Hofmeister  and  Schiitz,  cannot  be 
definitely  stated.  The  force  with  which  the  contents  of  the  antrum  are 
ejected  through  the  pylorus  into  the  duodenum,  as  shown  by  observations 
made  upon  animals  with  a  duodenal  fistula,  speaks  in  favor  of  the  latter 
view.  It  is  possible  that  either  of  these  phases,  but  especially  the  tirst, 
might  occur  at  times  without  the  other,  and  in  the  first  phase  it  is  probable 
that  the  longitudinal  fibres  of  the  stomach  also  contract,  shortening  the 
organ  in  its  long  diameter  and  aiding  in  the  propulsive  movement,  but 
actual  observation  of  this  factor  has  not  been  successfully  made.  It  can 
well  be  understood  that  a  series  of  these  movements  occurring  at  short  inter- 
vals would  result  in  putting  the  entire  semi-liquid  contents  of  the  stomach 
into  constant  circulation.  The  precise  direction  of  the  current  set  up  is  not 
agreed  upon,  but  it  is  probable  that  the  graphic  description  given  by  Beaumont 
is  substantially  accurate.  A  portion  of  this  description  may  be  quoted,  as  fol- 
lows :  "The  ordinary  course  and  direction  of  the  revolutions  of  the  food  are, 
first,  after  passing  the  oesophageal  ring,  from  right  to  left,  along  the  small 
arch;  thence,  through  the  large  curvature,  from  left  to  right.  The  bolus,  as  it 
eniers  the  cardia,  turns  to  the  left ;  passes  the  aperture ;  descends  into  the  splenic 
extremity,  and  follows  the  great  curvature  toward  the  pyloric  end.  It  then 
returns  in  the  course  of  the  small  curvature."  The  average  time  taken  for  one 
of  these  complete  revolutions,  according  to  observations  made  by  Beaumont, 
seems  to  vary   from   one  to  three  minutes. 

It  is  possible,  of  course,  thai  this  typical  circuit  taken  by  the  food  may  often 
be  varied  more  or  less  by  different  conditions,  but  the  muscular  movements 
observed  from  the  outside  would  seem  to  be  adapted  to  keeping  up  a  general 
revolution  of  the  kind  described.  The  general  result  upon  the  food  may  easily 
be  imagined.  It  becomes  thoroughly  mixed  with  the  gastric  juice  and  any  liquid 
which  may  have  been  swallowed,  and  is  gradually  disintegrated,  dissolved,  and 
more  or  less  completely  digested  so  far  as  the  proteid  and  albuminoid  constitu- 
ent- are  concerned.  The  mixing  action  is  aided,  moreover,  by  the  movements 
of  the  diaphragm  in  respiration,  since  at  each  de-cent  it  presses  upon  the  stomach. 
The  powerful  muscular  contractions  of  the  antrum  serve  also  to  triturate  the 
softened  solid  particle-,  and  finally  the  whole  mass  is  reduced  to  a  liquid  or 


MOVEMENTS   OF   THE  ALIMENTARY   CANAL,   ETC.        381 

semi-liquid  mixture  known  as  chyme,  and  in  this  condition  the  rhythmic 
contractions  of  the  muscles  of  the  antrum  eject  it  into  the  duodenum.  The 
rhythmic  spirting  of  the  contents  of  the  stomach  into  the  duodenum  lias 
been  noticed  by  a  number  of  observers  by  means  of  duodenal  fistulas  in  dogs, 
established  just  beyond  the  pylorus.  It  has  been  shown  also  that  when  the 
food  taken  is  entirely  liquid — water,  for  example — the  stomach  is  emptied  in  a 
surprisingly  short  time,  within  twenty  to  thirty  minutes  ;  if,  however,  the 
water  is  taken  with  solid  food  then  naturally  the  time  it  will  remain  in  the 
stomach  may  be  much  lengthened. 

A  very  interesting  part  of  the  mechanism  of  the  stomach  the  action  of 
which  is  not  thoroughly  understood  is  the  sphincter  of  the  pylorus.  During 
the  act  of  digestion  this  sphincter  remains  in  a  condition  of  tone ;  whether 
its  tonic  contraction  is  sufficient  only  to  narrow  the  pylorus,  or  whether  it 
is  sufficient  to  completely  shut  off  the  pylorus  so  that  a  partial  relaxation 
must  occur  with  each  contraction  of  the  musculature  of  the  antrum,  is  not 
sufficiently  well  known.  It  has  been  shown,  however,  that  this  part  of  the 
circular  layer  of  muscle  is  distinctly  under  the  control  of  the  extrinsic 
nerves,  its  tonicity  being  increased  by  impulses  received  through  the  vagi  and 
diminished  or  inhibited  by  impulses  through  the  splanchnics.  It  will  be  seen 
from  the  above  brief  description  that  the  muscles  of  the  antrum  pylori  do 
most  of  the  work  of  the  stomach,  while  in  the  much  larger  fundus  the  food 
is  retained  as  in  a  reservoir  to  be  digested  and  mechanically  prepared  for 
expulsion  into  the  intestine,  the  two  parts  of  the  stomach  fulfilling  therefore 
somewhat  different  functions.  Moritz l  has  called  especial  attention  to  this 
fact,  and  points  out  the  great  advantage  which  accrues  to  the  digestive  pro- 
cesses in  the  intestine  in  having  the  stomach  to  retain  the  bulk  of  the  food 
swallowed  during  a  meal,  while  from  time  to  time  small  portions  only  are 
sent  into  the  intestine  for  more  complete  digestion  and  absorption.  In  this 
way  the  intestine  is  protected  from  becoming  congested,  and  its  digestive  and 
absorptive  processes  are  more  perfectly  executed. 

Extrinsic  Nerves  to  the  Muscles  of  the  Stomach. —  The  musculature 
of  the  stomach  receives  extrinsic  nerve-fibres  from  two  sources:  from  the  two 
vagi  and  from  the  solar  plexus.  The  fibres  from  the  latter  source  arise  ulti- 
mately in  the  spinal  cord,  pass  to  some  of  the  thoracic  ganglia  of  the  sympa- 
thetic system,  and  thence  by  way  of  the  splanchnics  to  the  semilunar  <>r  solar 
plexus  and  then  to  the  stomach.  These  fibres  probably  reach  the  stomach  as 
non-medullated  or  sympathetic  fibres.  The  vagi  where  they  are  distributed 
to  the  stomach  seem  to  consisl  almosf  entirely  of  non-medullated  fibres  also, 
and  probably  the  fibres  distributed  to  the  muscular  coat  arc  of  this  variety. 
The  results  of  numerous  experiments  seem  to  show  quite  conclusively  thai  in 
general  the  fibres  received  along  the  vagus  path  arc  motor,  artificial  stimula- 
tion of  them  causing  mure  or  less  well  marked  contractions  of  part  or  all  of 
the  musculature  of  the  stomach.  It  has  been  shown  that  the  sphincter  pylori 
as  well  as  the  rest  of  the  musculature  is  supplied  by  motor  fibres  from  these 

1  Zeitschrift  filr  Biologie,  1895,  Bd.  xxxii. 


382  AN    AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

nerves.  The  fibres  coming  through  the  splanchnics,  on  the  contrary,  are 
mainly  inhibitory.  When  stimulated  they  cause  a  dilatation  of  the  contracted 
stomach  and  a  relaxation  of  the  sphincter  pylori.  Some  observers  have 
reported  experiments  which  seem  to  show  that  this  anatomical  separation  of 
the  motor  and  inhibitory  fibres  is  not  complete;  that  some  inhibitory  fibres 
may  be  found  in  the  vagi  and  some  motor  fibres  in  the  splanchnics.  The 
anatomical  courses  of  these  fibres  are  insufficiently  known,  but  there  seems  to 
lie  no  question  as  to  the  existence  of  the  two  physiological  varieties.  Through 
their  activity,  without  doubt,  the  movements  of  the  stomach  may  be  regu- 
lated, favorably  or  unfavorably,  by  conditions  directly  or  indirectly  affect- 
ing the  central  nervous  system.  Wertheimer1  has  shown  experimentally  that 
stimulation  of  the  central  end  of  the  sciatic  or  the  vagus  nerve  may  cause 
reflex  inhibition  of  the  tonus  of  the  stomach,  and  Doyon  2  has  confirmed  this 
result  in  cases  where  the  movements  and  tonicity  of  the  stomach  were  first 
increased  by  the  action  of  pilocarpin  and  strychnin.  Cannon  in  his  observa- 
tions upon  cat-  found  that  all  movements  of  the  stomach  ceased  as  soon  as 
the  animal  showed  signs  of  anxiety,  rage,  or  distress.  It  must  be  borne  in 
mind,  however,  that  the  action  of  these  extrinsic  fibres  under  normal  conditions 
is  probably  only  to  regulate  the  movements  of  the  stomach.  As  we  have 
seen,  even  the  extirpated  stomach  under  proper  conditions  seems  to  execute 
movements  of  the  normal  type.  Normally  the  movements  are  provoked  by  a 
stimulus  of  some  kind,  usually  the  presence  of  food  material  in  the  interior 
of  the  stomach.  How  the  stimulus  acts  in  this  case,  whether  directly  upon  the 
muscle-fibres  or  indirectly  through  the  intrinsic  ganglia  of  the  stomach,  has 
not  been  determined,  and  the  evidence  for  either  view  is  so  insufficient  that  a 
discussion  of  the  matter  at  this  time  would  scarcely  be  profitable.  We  musl 
wait  for  more  complete  investigations  upon  the  physiology  as  well  as  the  his- 
tology of  the  muscle-  and  nerve-tissue  in  this  and  in  other  visceral  organs 
constructed  on  the  same  type. 

Movements  op  the  Intestines. 

The  muscles  of  the  small  and  the  large  intestine  are  arranged  in  two  layers, 
an  outer  longitudinal  and  an  inner  circular  coat,  while  between  these  coats  and 
in  the  submucous  coat  there  are  present  the  nerve-plexuses  of  Auerbach  and 
Meissner.  The  general  arrangement  of  muscles  and  nerves  i<  similar,  there- 
fore, to  that  prevailing  in  the  stomach,  and  in  accordance  with  this  we  find  that 
the  physiological  activities  exhibited  are  of  much  the  same  character,  only,  per- 
haps not  quite  so  complex. 

Forms  of  Movement. — Two  main  forms  of  intestinal  movement  have  been 
distinguished,  the  peristaltic  and  the  pendular. 

Peristalsis. — The  peristaltic  movement  consists  in  a  constriction  of  the  walls 
of  the  intestine  which  beginning  at  a  certain  point  passes  downward  away  from 
the  stomach,  from  segmenl  to  segment,  while  the  parts  behind  the  advancing 
/.one  of  constriction  gradually  relax.     The  evident  effect  of  such  a  movement 

1  .i  PhysiologU  normak  et  pathologique,  1S92.  p.  379.  2  Ibid.,  1895,  p.  374. 


MOVEMENTS   OF   THE  ALIMENTARY   CANAL,    ETC        383 

would  be  to  push  onward  the  contents  of  the  intestines  in  the  direction  of  the 
movement.  It  is  obvious  that  the  circular  layer  of  muscles  is  chiefly  involved  in 
peristalsis,  since  constriction  can  only  be  produced  by  contraction  of  this  layer. 
To  what  extent  the  longitudinal  muscles  enter  into  the  movement  is  not  definitel  v 
determined.  The  term  " anti-peristalsis"  is  used  to  describe  the  same  form  of 
movement  running  in  the  opposite  direction — that  is,  toward  the  stomach. 
Anti-peristalsis  is  usually  said  not  to  occur  under  normal  conditions;  it  has 
been  observed  sometimes  in  isolated  pieces  of  intestine  or  in  the  exposed  intes- 
tine of  living  animals  when  stimulated  artificially,  and  Griitzner1  reports  a 
number  of  curious  experiments  which  seem  to  show  that  substances  such  as 
hairs,  animal  charcoal,  etc.,  introduced  into  the  rectum  may  travel  upward  to  the 
stomach  under  certain  conditions.  The  peristaltic  wave  normally  passes  down- 
ward, and  that  this  direction  of  movement  is  dependent  upon  some  definite 
arrangement  in  the  intestinal  walls  is  beautifully  shown  by  the  experiments  of 
Mall2  and  others  upon  reversal  of  the  intestines.  In  these  experiments  a  por- 
tion of  the  small  intestine  Mas  resected,  turned  round  and  sutured  in  place 
again,  so  that  in  this  piece  what  was  the  lower  end  became  the  upper  end. 
In  those  animals  that  made  a  good  operative  recovery  the  nutritive  condition 
gradually  became  very  serious,  and  in  the  animals  killed  and  examined  the 
autopsy  showed  accumulation  of  material  at  the  upper  end  of  the  reversed 
piece  of  intestine,  and  great  dilatation. 

The  peristaltic  movements  of  the  intestines  may  be  observed  upon  living 
animals  when  the  abdomen  is  opened.  If  the  operation  is  made  in  the  air 
and  the  intestines  are  exposed  to  its  influence,  or  if  the  conditions  of  tempera- 
ture and  circulation  are  otherwise  disturbed,  the  movements  observed  are 
often  violent  and  irregular.  The  peristalsis  runs  rapidly  along  the  intes- 
tines and  may  pass  over  the  whole  length  in  about  a  minute;  at  the  same  time 
the  contraction  of  the  longitudinal  muscles  gives  the  bowels  a  peculiar  writhing 
movement.  Movements  of  this  kind  are  evidently  abnormal,  and  onlv  occur 
in  the  body  under  the  strong  stimulation  of  pathological  conditions.  Normal 
peristalsis,  the  object  of  which  is  to  move  the  food  slowly  along  the  alimentary 
tract,  is  quite  a  different  affair.  Observers  all  agree  that  the  wave  of  contraction 
is  gentle  and  progresses  slowly.  According  to  Bayliss  and  Starling,3  the 
peristaltic  movement  is  a  complicated  reflex  through  the  intrinsic  ganglia. 
When  the  intestine  is  stimulated  by  a  bolus  placed  within  its  cavity,  the 
musculature  above  the  point  stimulated  is  excited,  while  that  below  is  in- 
hibited. In  accordance  with  this  law  they  find  that  in  peristalsis  the  advanc- 
ing wave  of  constriction  is  preceded  by  a  wave  of  relaxation  or  inhibition. 
The  force  of  the  contraction  as  measured  by  Cash  '  in  the  dog's  intestine  is 
very  small.  A  weighl  of  five  to  eight  grains  was  sufficient  to  check  the  on- 
ward movement  of  the  substance  in  the  intestine  and  to  set  up  violent  colicky 

1  Deutsche  medicinische   Wpchenschrift,  1894,  No.  18. 

2  The  Johns  Hopkins  Hospital  Reports,  vol.  i.  p.  93. 
8  Journal  of  Physiology,  L899,  vol    xxiv.  p.  99. 

4  Proceedings  of  tin-  Royal  Society,  London,  1887,  vol.  41. 


384  AN   AMERICA  X    TEXT-BOOK    OF  PHYSIOLOGY. 

contractions  which  caused  the  animal  evident  uneasiness.  We  may  suppose 
that  under  normal  conditions  each  contraction  of*  the  antrum  pylori  of  the 
stomach,  which  ejects  chyme  into  the  duodenum,  is  followed  by  a  peristalsis 
that  beginning  at  the  duodenum  passes  slowly  downward  for  a  part  or  all  of 
the  small  intestine.  According  to  most  observers,  the  movement  is  blocked 
at  the  ileo-ca?cal  valve,  and  the  peristaltic  movements  of  the  large  intestine 
form  an  independent  group  similar  in  all  their  general  characters  to  those  of 
the  small  intestine,  but  weaker  and  slower. 

Mechanism  of  the  Peristaltic  Movement. — The  means  by  which  the  peri- 
staltic movement  makes  its  orderly  forward  progression  have  not  been  deter- 
mined beyond  question.  The  simplest  explanation  would  be  to  assume  that 
an  impulse  is  conveyed  directly  from  cell  to  cell  in  the  circular  muscular 
coat,  so  that  a  contraction  started  at  any  point  would  spread  by  direct  con- 
duction of  the  contraction  change.  This  theory,  however,  does  not  explain 
satisfactorily  the  normal  conduction  of  the  wave  of  contraction  always  in  one 
direction,  nor  the  fact  that  a  reversed  piece  of  intestine  continues  to  send  its 
waves  in  what  was  fir  it  the  normal  direction.  Moreover,  Bayliss  and 
Starling  state  that  although  the  peristaltic  movements  continue  after  section 
of  the  extrinsic  nerves — indeed,  become  more  marked  under  these  conditions 
— the  application  of  cocaine  or  nicotine  prevents  their  occurrence.  Since  these 
substances  may  be  supposed  to  act  on  the  intrinsic  nerves,  it  is  probable 
that  the  co-ordination  of  the  movement  is  effected  through  the  local  nerve- 
ganglia,  but  our  knowledge  of  the  mechanism  and  physiology  of  these 
peripheral  nerve-plexuses  is  as  yet  quite  incomplete. 

Pendular  Movements. — In  addition  to  the  peristaltic  wave  a  second  kind 
of  movement  may  be  observed  in  the  exposed  intestines  of  a  living  animal. 
This  movement  is  characterized  by  a  gentle  swinging  to  and  fro  of  the  different 
loops,  whence  its  name  of  pendular  movement.  The  oscillations  occur  at 
regular  intervals,  and  are  usually  ascribed  to  rhythmic  contractions  of  the 
longitudinal  muscles.  Mall,1  however,  believes  that  the  main  feature  of  this 
movement  is  a  rhythmic  contraction  of  the  circular  muscles,  involving  a  part 
or  all  of  the  intestines.  He  prefers  to  speak  of  the  movements  as  rhythmic 
instead  of  pendular  contractions,  and  points  out  that  owing  to  the  arrangement 
of  the  blood-vessels  in  the  coats  of  the  intestine  the  rhythmic  contractions  should 
act  as  a  pump  to  expel  the  blood  from  the  submucous  venous  plexus  into  the 
radicles  of  the  superior  mesenteric  vein,  and  thus  materially  aid  in  keeping  up 
the  circulation  through  the  intestine  and  in  maintaining  a  good  pressure  in  the 
portal  vein,  in  much  the  same  way  as  happens  in  the  case  of  the  spleen  (see  p. 
332).  Bayliss  and  Starling  corroborate  this  view,  except  that  they  find  that 
both  the  circular  and  longitudinal  layers  of  muscle  are  concerned  in  the 
movement.  The  rhythmic  contractions,  according  to  these  observers,  are 
entirely  muscular  in  origin,  since  they  persist  after  the  application  of 
nicotine   or  cocaine. 

Extrinsic  Nerves  of  the  Intestines. — As  in  the  case  of  the  stomach,  the 
1  The  Johns  Hopkins  Hospital  Reports,  vol.  i.  p.  37. 


MOVEMENTS  OF  THE  ALIMENTARY   CANAL,   ETC.       385 

small  intestine  and  the  greater  part  of  the  large  intestine  receive  visceromotor 
nerve-fibres  from  the  vagi  and  the  sympathetic  chain.  The  former,  according 
to  most  observers,  when  artificially  stimulated  cause  movements  of  the  intestine, 
and  are  therefore  regarded  as  the  motor  fibres.  It  seems  probable,  however, 
that  the  vagi  carry  or  may  carry  in  some  animals  inhibitory  fibres  as  well,  and  that 
the  motor  effects  usually  obtained  upon  stimulation  aredue  to  the  fad  that  in  these 
nerves  the  motor  fibres  predominate.  The  fibres  received  from  the  sympathetic 
chain,  on  the  other  hand,  give  mainly  an  inhibitory  effect  when  stimulated, 
although  some  motor  fibres  apparently  may  take  this  path.  Bechterew  and 
Mislawski 1  state  that  the  sympathetic  fibres  for  the  small  intestine  emerge  from 
the  spinal  cord  as  medullated  fibres  in  the  sixth  dorsal  to  the  first  lumbar 
spinal  nerves,  and  pass  to  the  sympathetic  chain  in  the  splanchnic  nerves  and 
thence  to  the  semilunar  plexus,  while  the  sympathetic  fibres  to  the  large  intes- 
tine and  rectum  arise  in  the  four  lower  lumbar  and  the  three  upper  sacral  spinal 
nerves.  According  to  Langley  and  Anderson2  the  descending  colon  and  rec- 
tum receive  a  double  nerve-supply — first  from  the  lumbar  spinal  nerves  (second 
to  fifth),  the  fibres  passing  through  the  sympathetic  ganglia  and  the  inferior 
mesenteric  plexus  and  causing  chiefly  an  inhibition  ;  second,  through  the  sacral 
nerves,  the  fibres  passing  through  the  nervus  erigens  and  the  hypogastric  plexus 
and  causing  chiefly  contraction  of  the  circular  muscle. 

These  extrinsic  fibres  undoubtedly  serve  for  the  regulation  of  the  move- 
ments of  the  bowels  from  the  central  nervous  system  ;  conditions  which  influ- 
ence the  central  system,  either  directly  or  indirectly,  may  thus  affect  the  intesti- 
nal movements.  The  paths  of  these  fibres  through  the  central  nervous  system 
are  not  known,  but  there  are  evidently  connections  extending  to  the  higher 
brain-centres,  since  psychical  states  are  known  to  influence  the  movements  of  the 
intestine,  and  according  to  some  observers  stimulation  of  portions  of  the  cere- 
bral cortex  may  produce  movements  or  relaxation  of  the  walls  of  the  small  and 
large  intestines.  As  in  the  case  of  the  stomach,  the  extrinsic  fibres  seem  to 
have  only  a  regulatory  influence.  When  they  are  completely  severed  the 
tonicity  of  the  walls  of  the  intestine  is  not  altered,  and  peristaltic  and  rhythmic 
movements  still  occur.  The  same  results  may  be  obtained  even  upon  ex- 
cised portions  of  the  intestines  (Salvioli,  Mall).  It  seems  probable,  there- 
fore, that  normal  peristalsis  in  the  living  animal  may  be  effected  independently 
of  the  central  nervous  system,  although  its  character  and  strength  is  subject 
to  regulation  through  the  medium  of  the  viscero-motor  fibres,  in  much  the 
same  way,  and  possibly  t<>  as  great  an  extent,  as  the  movements  of  the  heart  are 
controlled  through  its  extrinsic  nerves. 

Effect  of  Various  Conditions  upon  the  Intestinal  Movements. —  Experi- 
ments have  shown  that  the  movements  of  the  intestines  may  be  evoked  in  many 
ways  beside  direct  stimulation  of  the  extrinsic  nerves.  Chemical  stimuli  may 
be  applied  directly  to  the  intestinal  wall.  Mechanical  stimulation,  pinching, 
for  example,  or  the   introduction  of  a  bolus  into  the   intestinal   cavity,  will 

1  Du  Bois-Reymond' a  Archiv  fur  Physiologic,  1889,  Suppl.  Bd. 
1  Journal  of  Physiology,  1895,  vol.  xviii.  p.  67. 

Vol..  I.— 25 


386  AX    AWERKAX    TEXT-BOOK    OF   PHYSIOLOGY. 

start  normal  peristalsis.  Violent  movements  may  be  produced  also  by  shut- 
ting off  the  blood-supply,  and  again  temporarily  when  the  supply  is  re-estab- 
lished. A  condition  of  dyspnoea  may  also  start  movements  in  the  intestines 
or  in  some  eases  inhibit  movements  which  are  already  in  progress,  the  stimu- 
lus in  this  ease  seeming  to  act  upon  the  central  nervous  system  and  to  stimu- 
late both  the  motor  and  the  inhibitory  fibres.  Oxygen  gas  within  the  bowels 
tend-  to  suspend  the  movements  of  the  intestine,  while  C02,  CH4,  and  H2S 
act  as  stimuli,  increasing  the  movements.  Organic  acids,  such  as  acetic, 
propionic,  formic,  and  caprylic,  which  may  be  formed  normally  within  the 
intestine  as  the  result  of  bacterial  action,  act  also  as  strong  stimulants.1 

Defecation. — The  undigested  and  indigestible  parts  of  the  food,  together 
with  some  of  the  debris  and  secretions  from  the  alimentary  tract,  are  carried 
slowly  through  the  large  intestine  by  its  peristaltic  movements  and  eventually 
reach  the  sigmoid  flexure  and  rectum.  Here  the  nearly  solid  material  stimu- 
lates by  its  pressure  the  sensory  nerves  of  the  rectum  and  produces  a  distinct 
sensation  and  desire  to  defecate.  The  fecal  material  is  retained  within  the  rectum 
by  the  action  of  the  two  sphincter  muscles  which  close  the  anal  opening.  One 
of  these  muscles,  the  internal  sphincter,  is  a  strong  band  of  the  circular  layer 
of  involuntary  muscles  which  forms  one  of  the  coats  of  the  rectum.  When 
the  rectum  contains  fecal  material  this  muscle  seems  to  be  thrown  into  a 
condition  of  tonic  contraction  until  the  act  of  defecation  begins,  when  it  is 
relaxed.  The  sphincter  is  composed  of  involuntary  muscle  and  is  innervated 
by  fibres  arising  partly  from  the  sympathetic  system,  and  in  part  through 
the  nervus  erigens,  from  the  sacral  spinal  nerves.  The  external  sphincter  ani 
is  composed  of  striated  muscle-tissue  and  is  under  the  control  of  the  will  to 
a  certain  extent.  When,  however,  the  stimulus  from  the  rectum  is  sufficiently 
intense,  voluntary  control  is  overcome  and  this  sphincter  is  also  relaxed. 
The  act  of  defecation  is  in  part  voluntary  and  in  part  involuntary.  The 
involuntary  factor  is  found  in  the  contractions  of  the  strongly  developed  mus- 
culature of  the  rectum,  especially  the  circular  layer,  which  serves  to  force  the 
feces  onward,  and  the  relaxation  of  the  internal  sphincter.  It  seems  that  these 
two  acts  are  mainly  caused  by  reflex  stimulation  from  the  lumbar  spinal  cord, 
although  it  is  probable  that  the  rectum,  like  the  rest  of  the  alimentary  tract, 
i-  capable  of  automatic  contractions.  The  rectal  muscles  receive  a  double 
nervous  supply,  containing  physiologically  both  motor  and  inhibitory  fibres. 
Some  of  these  fibres  come  from  the  nervus  erigens  by  way  of  the  hypogastric 
plexus,  and  some  arise  from  the  lumbar  cord  and  pass  through  the  correspond- 
in.:  sympathetic  ganglia,  inferior  mesenteric  ganglion,  and  hypogastric  nerve. 
It  has  been  asserted  that  stimulation  of  the  nervus  erigens  causes  contrac- 
tion of  the  longitudinal  muscles  and  inhibition  of  the  circular  muscles,  while 
stimulation  of  the  hypogastric  nerve  causes  contraction  of  the  circular  muscles 
and  inhibition  of  the  longitudinal  layer.  This  division  of  activity  is  not 
confirmed  by  the  recent  experiments  of  Langley  and  Anderson.2 

The  voluntary  factor  in  defecation  consist-  in  the  inhibition  of  the  external 
1  Buk;ii :  Archivfiir  exper.  PaihoLogie  und  Pharmakologie,  L888,  lid.  24,  S.  153.        2  Op.  eit. 


MOVEMENTS  OF  THE  ALIMENTARY   CANAL,   ETC       387 

sphincter  and  the  contraction  of  the  abdominal  muscles.  When  these  latter 
muscles  are  contracted  and  at  the  same  time  the  diaphragm  is  prevented  from 
moving  upward  by  the  closure  of  the  glottis,  the  increased  abdominal  pressure 
is  brought  to  bear  upon  the  abdominal  and  pelvic  viscera,  and  aids  strongly  in 
pressing  the  contents  of  the  descending  colon  and  sigmoid  flexure  into  the 
rectum.  The  pressure  in  the  abdominal  cavity  is  still  further  increased  it' 
a  deep  inspiration  is  first  made  and  then  maintained  during  the  contraction 
of  the  abdominal  muscles.  Although  the  act  of  defecation  is  normally  initiated 
by  voluntary  effort,  it  may  also  be  aroused  by  a  purely  involuntary  reflex  when 
the  sensory  stimulus  is  sufficiently  strong.  Goltz  1  has  shown  that  in  dogs 
in  which  the  spinal  cord  had  been  severed  in  the  lower  thoracic  region  defe- 
cation was  performed  normally.  In  later  experiments  in  which  the  entire 
spinal  cord  was  removed,  except  in  the  cervical  and  upper  part  of  the 
thoracic  region,  it  was  found  that  the  animal  after  it  had  recovered  from  the 
operation  had  normal  movement  once  or  twice  a  day,  indicating  that  the 
rectum  and  lower  bowels  acted  by  virtue  of  their  intrinsic  mechanism.  A 
curious  result  of  these  experiments  was  the  fact  that  the  external  sphincter 
eventually  regained  its  tonic  activity. 

It  would  seem  that  the  whole  act  of  defecation  is  at  bottom  an  involuntary 
reflex.  The  physiological  centre  for  the  movement  probably  lies  in  the  Lumbar 
cord,  and  has  sensory  and  motor  connections  with  the  rectum  and  the  muscles 
of  defecation,  but  this  centre  is  in  part  at  least  provided  with  connections  with 
the  centres  of  the  cerebrum  through  which  the  act  may  be  controlled  In- 
voluntary impulses  and  by  various  psychical  states,  the  effect  of  emotions 
upon  defecation  being  a  matter  of  common  knowledge.  In  infants  the  essen- 
tially involuntary  character  of  the  act  is  well  seen. 

Vomiting. — The  act  of  vomiting  causes  an  ejection  of  the  contents  of  the 
stomach  through  the  oesophagus  and  mouth  to  the  exterior.  It  was  long 
debated  whether  the  force  producing  this  ejection  comes  from  a  strong  contrac- 
tion of  the  walls  of  the  stomach  itself  or  whether  it  is  due  mainly  to  the 
action  of  the  walls  of  the  abdomen.  A  forcible  spasmodic  contraction  of  the 
abdominal  muscles  takes  place,  as  may  easily  be  observed  by  any  one  upon 
himself,  and  it  is  now  believed  that  the  contraction  of  these  muscles  is  the 
principal  factor  in  vomiting.  Magendie  found  that  if  the  stomach  was  extir- 
pated and  a  bladder  containing  water  was  substituted  in  its  place  and  connected 
with  the  oesophagus,  injection  of  an  emetic  caused  a  typical  vomiting  movement 
with  ejection  of  the  contents  of  the  bladder.  Giauuzzi  showed,  on  the  other 
hand,  that  upon  a  curarized  animal  vomiting  could  not  be  produced  by  an  emetic 
— because,  apparently,  the  muscles  of  the  abdomen  were  paralyzed  by  the  curare. 
There  are  on  record,  however,  a  number  of  observations  which  tend  to  show  thai 
the  stomach  is  not  entirely  passive  during  the  act.  <  >n  the  contrary,  it  may 
exhibit  contractions,  more  or  less  violent  in  character,  which  while  insufficient 
in  themselves  to  eject  its  contents,  probably  aid  in  a  normal  act  of  vomiting. 
According  to  <  )penchowski,2  the  pylorus  is  closed  and  the  pyloric  end  of  the 

1  Archiv  fiir  die  gesammte  Physiologie,  1874,  Bd.  viii.  8.  460;  also  Bd.  lxiii.  S.  362 

2  Archivfur  Physiologie,  1889,  S.  552. 


388  AN   AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

stomach  firmly  contracted  so  as  to  drive  the  contents  toward  the  dilated 
cardiac  portion.  The  act  of  vomiting  is  in  fact  a  complex  reflex  movement 
into  which  many  muscles  enter.  The  following  events  are  described  :  The 
vomiting  is  usually  preceded  by  a  sensation  of  nausea  and  a  reflex  How  of 
saliva  into  the  mouth.  These  phenomena  are  succeeded  or  accompanied  by 
retching  movements,  which  consist  essentially  in  deep  spasmodic  inspirations 
with  a  closed  glottis.  The  effect  of  these  movements  is  to  compress  the 
stomach  by  the  descent  of  the  diaphragm,  and  at  the  same  time  to  increase 
decidedly  the  negative  pressure  in  the  thorax,  and  therefore  in  the  thoracic 
portion  of  the  oesophagus.  During  one  of  these  retching  movements  the 
act  of  vomiting  is  effected  by  a  convulsive  contraction  of  the  abdominal 
wall  that  exert-  a  sudden  additional  strong  pressure  upon  the  stomach. 
At  the  same  time  the  cardiac  orifice  of  the  stomach  is  dilated,  possibly 
by  an  inhibition  of  the  sphincter,  aided  it  is  supposed  by  the  contrac- 
tion of  the  longitudinal  muscle-fibres  of  the  oesophagus  and  the  oblique 
fibres  of  the  muscular  coat  of  the  stomach.  The  stomach  contents  are, 
therefore,  forced  violently  out  of  the  stomach  through  the  oesophagus, 
the  negative  pressure  in  the  latter  probably  assisting  in  the  act.  The  pas- 
sage  through  the  oesophagus  is  effected  mainly  by  the  force  of  the  contrac- 
tion of  the  abdominal  muscles;  there  is  no  evidence  of  antiperistaltic  move- 
ments on  the  part  of  the  oesophagus  it-elf.  During  the  ejection  of  the  contents 
of  the  stomach  the  glottis  i-  kepi  closed  by  the  adductor  muscles,  and  usually 
the  nasal  chamber  is  likewise  shut  off  from  the  pharynx  by  the  contraction  of 
the  posterior  pillars  of  the  fauces  on  the  palate  and  uvula.  In  violent  vomit- 
ing, however,  the  vomited  material  may  break  through  this  latter  barrier  aud 
be  ejected  partially  through  the  nose. 

Nervous  Mechanism  <>f  Vomiting. — That  vomiting  is  a  reflex  act  is  abun- 
dantly shown  by  the  frequency  with  which  it  is  produced  in  consequence  of 
the  stimulation  of  sensory  nerves  or  as  the  result  of  injuries  to  various  [tarts 
of  the  central  nervous  system.  After  lesions  or  injuries  of  the  brain  vomiting 
often  results.  Disagreeable  emotions  and  disturbances  of  the  sense  of  equi- 
librium may  produce  the  same  result.  Irritation  of  the  mucous  membrane 
of  various  parts  of  the  alimentary  canal  (as,  for  example,  tickling  the  back 
of  the  pharynx  with  the  finger),  disturbances  of  the  urogenital  apparatus, 
artificial  stimulation  of  the  trunk  of  the  vagus  and  of  other  sensory  nerves, 
may  all  cause  vomiting.  Under  ordinary  conditions,  however,  irritation  of 
the  sensory  uerves  of  the  gastric  mucous  membrane  is  the  most  common 
cause  of  vomiting.  This  effecf  may  result  from  the  product- of  fermentation 
in  the  stomach  in  cases  of  indigestion,  or  may  be  produced  intentionally  by 
local  emetics,  such  as  mustard,  taken  into  the  stomach.  The  afferent  path 
in  this  case  is  through  the  sensory  fibres  of  the  vagus.  The  efferent  paths 
of  the  reflex  are  found  in  the  motor  nerves  innervating  the  muscles  con- 
cerned in  the  vomiting,  namely,  the  vagus,  the  phrenic-,  and  the  spinal  nerves 
supplying  the  abdominal  muscles.  Whether  or  not  there  is  a  definite  vomit- 
in-   centre  in   which   the  afferent   impulses   are   received  and   through   which 


3IOVE3IEXTS   OF  THE  ALIMENTARY   CANAL,  ETC.       389 

a  co-ordinated  series  of  efferent  impulses  is  sent  out  to  the  various  muscles, 
has  not  been  satisfactorily  determined.  It  has  been  shown  that  the  portion 
of  the  nervous  system  through  which  the  reflex  is  effected  lies  in  the  me- 
dulla. But  it  has  been  pointed  out  that  the  muscles  concerned  in  the  act 
are  respiratory  muscles.  Vomiting  in  fact  consists  essentially  in  a  simul- 
taneous spasmodic  contraction  of  expiratory  (abdominal)  muscles  and  inspi- 
ratory muscles  (diaphragm).  It  has  therefore  been  suggested  that  the  reflex 
takes  place  through  the  respiratory  centre,  or  some  part  of  it.  This  view 
seems  to  be  opposed  by  the  experiments  of  Thumas,1  who  has  shown  that 
when  the  medulla  is  divided  down  the  mid-line  respiratory  movements  con- 
tinue as  usual,  but  vomiting  can  no  longer  be  produced  by  the  use  of  emetics. 
Thumas  claims  to  have  located  a  vomiting  centre  in  the  medulla  in  the  imme- 
diate neighborhood  of  the  calamus  scriptorius.  Further  evidence,  however, 
is  required  upon  this  point.  The  act  of  vomiting  may  be  produced  not  only 
as  a  reflex  from  various  sensory  nerves,  but  may  also  be  caused  by  direct 
action  upon  the  medullary  centres.  The  action  of  apomorphia  is  most  easily 
explained  by  supposing  that  it  acts  directly  on  the  nerve-centres. 

Micturition. — The  urine  is  secreted  continuously  by  the  kidneys,  is  car- 
ried to  the  bladder  through  the  ureters,  and  is  then  at  intervals  finally  ejected 
from  the  bladder  through  the  urethra  by  the  act  of  micturition. 

Movements  of  the  Ureters. — The  ureters  possess  a  muscular  coat  consisting  of 
an  internal  longitudinal  and  external  circular  layer.  The  contractions  of  this 
muscular  coat  are  the  means  by  which  the  urine  is  driven  from  the  pelvis  of  the 
kidney  into  the  bladder.  The  movements  of  the  ureter  have  been  carefully 
studied  by  Engelmann.2  According  to  his  description  the  musculature  of  the 
ureter  contracts  spontaneously  at  intervals  of  ten  to  twenty  seconds  (rabbit),  the 
contraction  beginning  at  the  kidney  and  progressing  toward  the  bladder  in  the 
form  of  a  peristaltic  wave  and  with  a  velocity  of  about  twenty  to  thirty  milli- 
meters per  second.  The  result  of  this  movement  should  be  the  forcing  of  the 
urine  into  the  bladder  in  a  series  of  gentle  rhythmic  spirts,  and  this  method  of 
filling  the  bladder  has  been  observed  in  the  human  being.  Suter  and  Maver3 
report  some  observations  upon  a  boy  in  whom  there  was  ectopia  of  the  bladder 
with  exposure  of  the  orifices  of  the  ureters.  The  flow  into  the  bladder  was 
intermittent  and  was  about  equal  upon  the  two  sides  for  the  time  the  child 
was  under  observation  (three  and  a  half  days). 

The  causation  of  the  contractions  of  the  ureter  musculature  is  not  easily 
explained.  Engelmann  finds  that  artificial  stimulation  of  the  ureter  or  of  a 
piece  of  the  ureter  may  start  peristaltic  contractions  which  move  in  both  direc- 
tions from  the  point  stimulated.  lb'  was  not  able  to  find  ganglion-cells  in  the 
upper  two-thirds  of  the  ureter,  and  was  led  to  believe,  therefore,  that  the  con- 
traction originates  in  the  muscular  tissue  independently  of  extrinsic  or  intrinsic 
nerves,  and  that  the  contraction  wave  propagates  itself  directly  from   muscle- 

1  Virchovfs  Archiv  fur  pathologische  Anatornie,  etc.,  L891,  Bd.  123,  S.   II. 

"  PfiUgerl8  Archivfiir  diegesammte  Physiologie,  1869,  Bd.  ii.  B.  243;   Bd.  iv.  S.  33. 

3  Archiv  fiir  exper.  Patholog'x-  vmd  Pharmakologie,  1893,  Bd.  32,  S.  241. 


390  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

cell  to  muscle-cell,  the  entire  musculature  behaving  as  though  it  were  a  single, 
colossal  hollow  muscle-fibre.  The  liberation  of  the  stimulus  which  inaugurates 
the  normal  peristalsis  of  the  ureter  seems  to  be  connected  with  the  accumulation 
of  urine  in  its  upper  or  kidney  portion.  It  maybe  supposed  that  the  urine 
that  collects  at  this  point  as  it  flows  from  the  kidney  stimulates  the  muscular 
ti~-ue  to  contraction,  either  by  its  pressure  or  in  some  otherway,  and  thus  leads 
to  an  orderly  sequence  of  contraction  waves.  It  is  possible,  however,  that  the 
muscle  of  the  ureter,  like  that  of  the  heart,  is  spontaneously  contractile  under 
normal  conditions,  and  does  not  depend  upon  the  stimulation  of  the  urine. 
Thus,  according  to  Engelmann,  section  of  the  ureter  near  the  kidney  does  not 
materially  affect  the  nature  of  the  contractions  of  the  stump  attached  to  the 
kidney,  although  in  this  case  the  pressure  of  the  urine  could  scarcely  act  as  a 
stimulus.  Moreover,  in  the  case  of  the  rat,  in  which  the  ureter  is  highly  con- 
tractile, the  tube  may  be  cut  into  several  pieces  and  each  piece  will  continue  to 
exhibit  periodic  peristaltic  contractions.  It  does  not  seem  possible  at  present 
to  decide  between  these  two  views  as  to  the  cause  of  the  contractions.  The 
nature  of  the  contractions,  their  mode  of  progression,  and  the  way  in  which 
they  force  the  urine  through  the  ureter  seem,  however,  to  be  clearly  established. 
Efforts  to  show  a  regulatory  action  upon  these  movements  through  the  central 
nervous  system  have  so  far  given  only  negative  results. 

Movements  of  the  Bladder. — The  bladder  contains  a  muscular  coat  of  plain 
muscle-tissue,  which,  according  to  the  usual  description,  is  arranged  so  as  to 
make  an  external  longitudinal  coat  and  an  internal  circular  or  oblique  coat. 
A  thin  longitudinal  layer  of  muscle-tissue  lying  to  the  interior  of  the  circular 
coat  is  also  described.  The  separation  between  the  longitudinal  and  circular 
layers  is  not  so  definite  as  in  the  case  of  the  intestine ;  they  seem,  in  fact,  to  form 
a  continuous  layer,  one  passing  gradually  into  the  other  by  a  change  in  the 
direction  of  the  fibres.  At  the  cervix  the  circular  layer  is  strengthened,  and 
has  been  supposed  t<>  act  as  a  sphincter  with  regard  to  the  urethral  orifice — the 
so-called  sphincter  vesicae  internus.  Round  the  urethra  just  outside  the  blad- 
der is  a  circular  layer  <>f  striated  muscle  that  is  frequently  designated  as 
the  external  sphincter  or  sphincter  urethra'.  The  urine  brought  into  the 
bladder  accumulates  within  its  cavity  to  a  certain  limit.  It  is  prevented  from 
escaping  through  the  urethra  at  first  by  the  mere  elasticity  of  the  parts  at  the 
urethral  orifice,  aided  perhaps  by  tunic  contraction  of  the  internal  sphincter, 
although  this  function  of  the  circular  layer  is  disputed  by  some  observers. 
When  the  accumulation  becomes  greater  the  external  sphincter  is  brought  into 
action.  If  the  desire  to  urinate  is  strong  the  external  sphincter  seems  undoubt- 
edly to  be  controlled  by  voluntary  effort,  but  whether  or  not,  in  moderate  filling 
of  the  bladder,  it  is  brought  into  play  by  an  involuntary  reflex  is  not  definitely 
determined.  Back-flow  of  urine  from  the  bladder  into  the  ureters  is  effectually 
prevented  by  the  oblique  course  of  the  ureters  through  the  wall  of  the 
bladder.  Owing  to  this  circumstance  pressure  within  the  bladder  serves  to  close 
the  mouths  of  the  ureters,  and  indeed  the  more  completely  the  higher  the  pres- 
sure.    At  some  point   in  the  filling  of  the  bladder  the  pressure  is  sufficient  to 


MOVEMENTS   OF   Till-:  ALIMENTARY  CANAL,    ETC.        391 

arouse  a  conscious  sensation  of  fulness  and  a  desire  to  micturate.  Under  nor- 
mal conditions  the  act  of  micturition  follows.  It  consists  essentially  in  a  strong 
contraction  of  the  bladder  with  a  simultaneous  relaxation  of  the  external 
sphincter,  if  this  muscle  is  in  action,  the  effect  of  which  is  to  obliterate  more  or 
less  completely  the  cavity  of  the  bladder  and  drive  the  urine  out  through  the 
urethra. 

The, force  of  this  contraction  is  considerable,  as  is  evidenced  by  the  height 
to  which  the  urine  may  spirt  from  the  end  of  the  urethra.  According  to 
Mosso  the  contraction  may  support,  in  the  dog,  a  column  of  liquid  two  meters 
high.  The  contractions  of  the  bladder  may  be  and  usually  are  assisted  by 
contractions  of  the  walls  of  the  abdomen,  especially  toward  the  end  of  the  act. 
As  in  defecation  and  vomiting,  the  contraction  of  the  abdominal  muscles,  when 
the  glottis  is  closed  so  as  to  keep  the  diaphragm  'fixed,  serves  to  increase  the 
pressure  in  the  abdominal  and  pelvic  cavities,  and  is  thus  used  to  assist  in  or 
complete  the  emptying  of  the  bladder.  It  is,  however,  not  an  essential  part  of 
the  act  of  micturition.  The  last  portions  of  the  urine  escaping  into  the  urethra 
are  ejected,  in  the  male,  in  spirts  produced  by  the  rhythmic  contractions  of  the 
bulbo-cavernosus  muscle. 

Considerable  uncertainty  and  difference  of  opinion  exists  as  to  the  physio- 
logical mechanism  by  which  this  series  of  muscular  contractions,  and  especially 
the  contractions  of  the  bladder  itself,  is  produced.  According  to  the  frequently 
quoted  description  given  by  Goltz1  the  series  of  events  is  as  follows  :  The  dis- 
tention of  the  bladder  by  the  urine  causes  finally  a  stimulation  of  the  sensory 
fibres  of  the  organ  and  produces  a  reflex  contraction  of  the  bladder  musculature 
which  squeezes  some  urine  into  the  urethra.  The  first  drops,  however,  that 
enter  the  urethra  stimulate  the  sensory  nerves  there  and  give  rise  to  a  conscious 
desire  to  urinate.  If  no  obstacle  is  presented  the  bladder  then  empties  itself, 
assisted  perhaps  by  the  contractions  of  the  abdominal  muscles.  The  emptying 
of  the  bladder  may,  however,  be  prevented,  if  desirable,  by  a  voluntary  con- 
traction of  the  sphincter  urethra,  which  opposes  the  effect  of  the  contraction  of 
the  bladder.  If  the  bladder  is  not  too  full  and  the  sphincter  is  kept  in  action 
for  some  time,  the  contractions  of  the  bladder  may  cease  and  the  desire  to 
micturate  pass  off.  According  to  this  view  the  voluntary  control  of  the 
process  is  limited  to  the  action  of  the  external  sphincter  and  the  abdominal 
muscles;  the  contraction  of  the  bladder  itself  is  purely  an  unconscious  reflex 
taking  place  through  a   lumbar  centre. 

The  experiments  of  Goltz  and  others,  upon  dogs  in  which  the  spinal  cord 
was  severed  at  the  junction  of  the  lumbar  and  the  thoracic  regions,  indicate 
that  micturition  is  essentially  a  reflex  acl  with  it.-  centre  in  the  lumbar  cord, 
although  the  same  observer  has  shown  that  in  dogs  whose  spinal  cord  has 
been  entirely  destroyed,  except  in  the  cervical  and  upper  thoracic  region,  the 
bladder  empties  itself  normally  without  the  aid  of  external  stimulation. 
MoSSO  and    Pellacani 2  have   made   experiments   upon  women  which    ><'r\\\   to 

1  Archiv fur  die  gesammte  Physiologie,  IsTt,  Bd,  viii.  S.  17s 

2  Archives  it<tli<  nii>.<  ,h   Biologie,  L882,  tome  i. 


392  AN   AMERICAN   TEXT-BOOK   OF   PHYSIOLOGY. 

show  thai  the  bladder  may  be  emptied  by  a  direci  voluntary  act.  Tn  these 
experiments  a  catheter  was  introduced  into  the  bladder  and  connected  with 

a  r< rding  apparatus  to  measure  the  volume  of  the  bladder.     It  was  found 

that,  in  some  cases  at  least,  the  woman  could  empty  the  bladder  at  will 
without  using  the  abdominal  muscles.  The  same  authors  adduce  experi- 
mental evidence  to  show  that  the  sensation  of  fulness  and  desire  to  mic- 
turate come  from  sensory  stimulation  in  the  bladder  itself  caused  by  the 
pressure  of  the  urine.  They  point  out  that  the  Madder  is  very  sensitive  to 
reflex  stimulation  ;  that  every  psychical  act  and  every  sensory  stimulus  is 
apt  to  cause  a  contraction  or  increased  tone  of  the  bladder.  The  Madder  is, 
therefore.  subject  t<>  eoiitiiiual  changes  in  size  from  reflex  stimulation,  and 
the  pressure  within  it  will  depend  not  simply  on  the  quantity  of  urine,  but 
■  m  the  condition  of  tone  of  the  bladder.  At  a  certain  pressure  the  sen- 
sorv  nerves  are  stimulated  and  under  normal  conditions  micturition  ensues. 
We  may  understand,  from  this  point  of  view,  how  it  happens  that  we  have 
sometimes  a  strong  desire  to  micturate  when  the  bladder  contains  bui  little 
urine — for  example,  under  emotional  excitement.  In  such  cases  if  the  micturi- 
tion is  prevented,  probably  by  the  action  of  the  external  sphincter,  the  bladder 
may  subsequently  relax  and  the  sensation  of  fulness  and  desire  to  micturate 
pass  away  until  the  urine  accumulates  in  sufficient  quantity  or  the  pressure  is 
again  raised  by  some  circumstance  which  causes  a  reflex  contraction  of  the 
bladder. 

\<  rvous  Mechanism. — According  to  a  recent  paper  by  Langley  and  Anderson,1 
the  bladder  in  cats,  dogs,  and  rabbits  receives  motor  fibres  from  two  sources:  (1) 
From  the  lumbar  nerves,  the  fibres  passing  out  in  the  second  to  the  fifth  lumbar 
nerves  and  reaching  the  bladder  through  the  sympathetic  chain  and  the  infe- 
rior mesenteric  ganglion  and  hypogastric  nerves.  Stimulation  of  these  nerves 
causes  comparatively  feeble  contraction  of  the  bladder.  (2)  From  the  sacral 
spinal  nerves,  the  fibre-  originating  in  the  second  and  third  sacral  spinal  nerves, 
or  in  the  rabbit  in  the  third  and  fourth,  and  being  contained  in  the  so-called 
nervus  erigens.  Stimulation  of  these  nerves,  or  some  of  them,  causes  strong 
contractions  of  the  bladder,  sufficient  to  empty  its  contents.  Little  evidence 
was  obtained  of  the  presence  of  vaso-motor  fibres.  According  to  Nawrocki 
and  Skabitschewsky a  the  spinal  sensory  fibre-  to  the  bladder  are  found  in  part 
in  the  posterior  roots  of  the  first,  second, third,  and  fourth  sacral  spinal  nerves, 
particularly  the  second  and  third.  When  these  fibres  are  stimulated  they  excite 
reflexly  the  motor  fibres  to  the  bladder  found  in  the  anterior  roots  of  the  second 
and  third  sacral  spinal  nerves.  Some  sensory  fibres  to  the  bladder  pass  by  way 
of  the  hypogastric  nerves.  When  these  are  stimulated  they  produce,  according 
to  these  authors,  a  reflex  effect  upon  the  motor  fibres  in  the  other  hypogastric 

nerve,  causing  a  < traction  of  the  bladder,  the  reflex  occurring  through   the 

inferior  mesenteric  ganglion.  This  observation  has  been  confirmed  by  several 
authorities,  and  is  the  best  example  of  a  peripheral  ganglion  serving  as  a  reflex 

'-  Journal  of  Phyxiolgy,  1895,  vol.  xix.  p.  71. 

-  Archivfur  <H>  gesamnUe  Physiologic,  1891,  Bd.  49,  S.  141. 


MOVEMENTS   OF   THE  ALIMENTARY   (ANAL,    ETC.        393 

centre.  Langley  and  Anderson,1  who  also  obtained  this  effect,  give  it  a  special 
explanation,  contending  that  it  is  not  a  true  reflex. 

The  immediate  spinal  centre  through  which  the  contractions  of  the  bladder 
may  be  reflex ly  stimulated  or  inhibited  lies,  according  to  the  experiments  of 
Goltz,  in  the  lumbar  portion  of  the  cord,  probably  between  the  second  and  fifth 
lumbar  spinal  nerves.  In  dogs  in  which  this  portion  of  the  cord  was  isolated 
by  a  cross  section  at  the  junction  of  the  thoracic  and  lumbar  regions,  micturi- 
tion still  ensued  when  the  bladder  was  sufficiently  full,  and  could  be  called 
forth  reflexly  by  sensory  stimuli,  especially  by  slight  irritation  of  the  anal 
region.     This  localization  has  been  confirmed  by  others.2 

Movements  of  other  Visceral  Organs. — For  the  characteristics  of  the  move- 
ments of  other  viscera  reference  must  be  made  to  the  appropriate  sections. 
The  movements  of  the  arteries  are  described  under  Circulation,  those  of  the 
uterus  under  Reproduction. 

1  Journal  of  Physiology,  1894,  vol.  xvi.  p.  410;  see  also  Justschenko :  Archives  des  Sciences 
biologiques,  1898,  t.  6,  p.  536. 

2  See  .Stewart:   American  Journal  of  Physiology,  1899,  vol.  ii.  p.  182. 


VII.  RESPIRATION. 


A  study  of  the  phenomena  of  animal  life  teaches  us  that  a  supply  of 
oxygen  and  an  elimination  of  carbon  dioxide  are  essential  to  existence.  Oxy- 
gen is  indispensable  to  life;  carbon  dioxide  is  inimical  to  life.  One  serves  for 
the  disintegration  of  complex  molecules  whereby  energy  is  evolved,  while  the 
other  is  one  of  the  main  effete  products  of  this  dissociation.  We  therefore  find 
an  intimate  relationship  between  the  ingress  of  the  one  and  the  egress  of  the 
other.  During  the  entire  life  of  the  individual  there  is  this  continual  inter- 
change, which  we  term  respiration.  This  term  embraces  two  acts  which,  while 
different,  are  nevertheless  co-operative — first,  the  interchange  of  O  and  C02 ; 
second,  the  movements  of  certain  parts  of  the  body,  having  for  their  object  the 
inflow  and  outflow  of  air  to  and  from  the  lungs.  The  former,  properly  speak- 
ing, is  respiration  ;  the  latter,  movements  of  respiration. 

Respiration  is  spoken  of  as  internal  and  as  external  respiration.  In  the 
very  lowest  forms  of  life  the  interchange  of  gases  takes  place  directly  between 
the  various  parts  of  the  organism  and  the  air  or  the  water  in  which  the  organ- 
ism lives ;  but  in  higher  beings  a  circulating  fluid  becomes  a  means  of 
exchange  between  the  bodily  structures  and  the  surrounding  medium,  so  that 
in  these  beings  there  is  first  an  interchange  between  the  air  or  the  water  in 
which  the  animal  lives  and  the  circulating  medium,  and  subsequently  an  inter- 
change between  the  circulating  medium  and  the  tissues.  Therefore  in  the  most 
primitive  forms  of  life  respiration  is  a  single  process,  while  in  higher  organ- 
isms it  is  a  dual  process,  or  one  consisting  of  two  stages,  the  first  being  the 
interchange  between  the  atmosphere  or  the  water  surrounding  the  body  and 
the  circulating  medium,  and  the  second  between  the  circulating  medium  and 
the  bodily  structures.  In  man,  external  respiration  is  the  interchange  taking 
place  between  the  blood  and  the  gases  in  the  lungs  and.  to  a  very  small 
extent,  between  the  blood  and  the  air  through  the  skin  ;  while  internal  res- 
piration is  the  interchange  between  the  blood  and  the  tissues.  In  external 
respiration  O  is  absorbed  and  (  '(  )_,  is  given  off  by  the  blood  :  in  internal  res- 
piration the  blood  absorbs  ( '()._,  and  gives  off  O. 

A.  The  Respiratory  Mechanism  in  Man. 

The  respiratory  apparatus  in  man  consists  (1)  of  the  lungs  and  the  air- 
passages  loading  to  them,  the  thorax  and  the  mnsenlar  mechanisms  by  means 
of  which  the  lungs  are  inflated  and  emptied,  and  the  nervous  mechanisms  con- 
nected therewith  ;  and  (2)  the  skin,  which,  however,  plays  a  subsidiary  part  in 
man,  and  need  not  here  be  considered. 

395 


396  IV   AMERICAN    Tl 'XT-BOOK   OF  PHYSIOLOGY. 

The  lungs  may  be  regarded  as  two  large  bags  broken  up  into  saccular 
divisions  and  subdivisions  which  ultimately  consist  of  a  vast  number  of  little 
pouches,  or  infundibuli,  each  of  which  is,  as  the  name  implies,  funnel-shaped, 
the  walls  being  hollowed  out  into  alveoli,  or  air- vesicles.  These  alveoli  vary 
in  size  from  120  ju  to  380 /i,  the  average  diameter  being  about  250//  (y^  inch). 
Each  infundibulum  communicates  by  means  of  a  small  air-passage  with  a 
bronchiole,  which  in  turn  communicates  with  a  smaller  air-tube  or  bronchus, 
and  finally,  through  successive  unions,  with  the  common  air-duct  or  trachea. 
It  i<  estimated  that  the  alveoli  number  about  725,000,000,  and  that  the  total 
superficies  exposed  by  them  to  the  gases  in  the  lungs  is  about  200  square 
meters,  or  from  one  hundred  to  one  hundred  and  thirty  times  greater  than 
the  surface  of  the  body  ( L.5  to  2  square  meters).  The  wall  of  each  alveolus 
forms  a  delicate  partition  between  the  air  in  the  lungs  and  an  intricate  net- 
work of  blood-vessels;  this  network  is  so  dense  that  the  spaces  between  the 
capillaries  an;,  as  a  rule,  smaller  than  the  diameters  of  the  vessels.  The 
lungs,  therefore,  are  exceedingly  vascular,  and  it  is  estimated  that  the  vessels 
contain  on  an  average  about  1.5  kilograms  of  blood.  Owing  to  the  minute- 
ness  of  the  capillaries  and  the  density  of  the  network,  the  air-cells  may  be 
said  to  be  surrounded  by  a  film  of  blood  which  is  about  10/v  in  thickness  and 
has  an  area  of  about  150  square  meters. 

The  lungs  are  highly  elastic,  and  their  elasticity  is  perfect,  as  is  shown  by 
the  fact  that  they  immediately  regain  their  passive  condition  as  soon  as  the 
dilating  or  distending  force  has  been  removed.  Before  birth  the  lungs  are  air- 
less  (iihlci-l(tt'ic)  and  the  walls  of  the  bronchioles  and  the  infundibuli  are  in 
contact,  yet  in  the  child  before  birth,  as  in  the  adult,  the  lungs  are  in  apposi- 
tion with  the  thoracic  walls,  being  separated  only  by  two  layers  of  the  pleurae. 
As  soon  as  the  child  is  born  a  few  respiratory  movements  are  sufficient  to 
inflate  them,  and  thereafter  they  never  regain  their  atelectatic  condition,  since 
after  the  most  complete  collapse,  such  as  occurs  when  the  thorax  is  opened, 
some  air  remains  in  the  alveoli,  owing  to  the  fact  that  the  walls  of  the  bron- 
chioles come  together  before  all  of  the  air  can  escape.  As  the  child  grows  the 
thorax  increases  in  size  more  rapidly  than  the  lungs,  and  becomes  too  large,  as 
it  were,  for  the  lungs,  which,  as  a  consequence,  become  permanently  distended 
because  of  their  being  in  an  air-tight  cavity.  If  the  chest  of  a  cadaver  be 
punctured,  the  lungs  immediately  -brink  so  that  a  considerable  air-space  will 
be  formed  between  them  and  the  walls  of  the  thorax.  This  collapse  is  due  to 
the  condition  of  elastic  ten-ion  which  exists  from  the  moment  air  is  introduced 
into  the  alveoli,  and  which  increases  with  the  degree  of  expansion.  Therefore, 
after  the  lungs  are  inflated  they  exhibit  a  persistent  tendency  to  collapse;  con- 
sequently they  musl  exercise  upon  the  thoracic  walls  and  diaphragm  a  constant 
traction  or  "pull"  which  is  in  proportion  to  the  amount  of  tension.  It  is 
therefore  obvious  that  there  musl  exisl  within  the  thorax,  under  ordinary 
circumstances,  a  state  of  ncr/utive  pressure  (pressure  below  that  of  the  atmo- 
sphere). This  can  be  proven  by  connecting  a  trocar  with  a  manometer  and 
then  forcing  the  trocar  into  one  of  the  pleural  sacs. 


BESPIRA  TION  397 

Donders  found  that  the  pressure  at  the  end  of  quiet  expiration  was  —6  mil- 
limeters of  Hg,  and  at  the  end  of  quiet  inspiration  —9  millimeters.  Accord- 
ing to  these  figures,  the  pressure  on  the  heart,  great  blood-vessels,  and  other 
thoracic  structures  lying  between  the  lungs  and  the  thoracic  walls  would  be 
754  millimeters  of  Hg  (one  atmosphere,  760  millimeters,  —6  millimeters)  at 
the  end  of  quiet  expiration,  and  751  millimeters  of  Hg  at  the  end  of  quiet 
inspiration.  Corresponding  values  by  Hutchinson  are  —3  millimeters  and 
—4.5  millimeters.  Arron  x  found  in  a  case  of  a  woman  with  emphysema  that 
the  pressure  at  the  end  of  expiration  ranged  from  —1.9  to  —3.9  millimeters, 
and  at  the  end  of  inspiration  from  —4  to  —6.85  millimeters,  according  to  the 
position  of  the  body,  the  pressure  being  lowest  in  the  lying  posture,  higher 
when  sitting  in  bed,  still  higher  when  sitting  on  a  chair,  and  highest  when  sit- 
ting and  when  inspiration  on  the  well  side  was  hindered,  thus  throwing  a  larger 
portion  of  the  work  on  the  diseased  side,  on  which  the  measurements  were 
made.  During  inspiration  negative  pressure  increases  in  proportion  to  the 
depth  of  inspiration — or,  in  other  words,  in  relation  to  the  amount  of  expan- 
sion of  the  lungs — while  during  expiration  it  gradually  falls  to  the  standard  at 
the  beginning  of  inspiration.  During  forced  inspiration  it  may  reach  —30  to 
—40  millimeters  or  more.  The  pressure  thus  observed  within  the  thorax  (out- 
side of  the  lungs)  is  known  as  intrathoracic  pressure,  and  must  not  be  con- 
founded with  intrapulmonary  or  respiratory  pressure,  which  exists  within  the 
lungs  and  the  respiratory  passages  (see  p.  408). 

The  thorax  is  capable  of  enlargement  in  all  directions.  It  is  cone-shaped, 
the  top  of  the  cone  being  closed  in  by  the  structures  of  the  neck ;  the  sides, 
by  the  vertebral  column,  ribs,  costal  cartilages,  sternum,  and  intercostal  sheets 
of  muscular  and  other  tissues;  and  the  bottom,  by  the  arched  diaphragm.  It 
is  obvious  that,  since  the  thorax  is  an  air-tight  cavity  and  completely  filled 
by  various  structures,  enlargement  in  any  direction  must  cause  a  diminution  of 
pressure  within  the  lungs,  while  a  shrinkage  would  operate  to  bring  about  an 
opposite  condition  of  increased  pressure.  Since  the  trachea  is  the  only  means  of 
communication  between  the  lungs  and  the  atmosphere,  it  is  evident  that  such 
alterations  in  pressure  must  encourage  either  the  inflow  or  the  outflow  of  air,  as 
the  case  may  be;  consequently,  when  the  thoracic  cavity  is  expanded  the  pres- 
sure within  the  lungs  is  less  than  that  of  the  atmosphere,  and  air  is  forced  into 
the  lungs;  and  when  the  thorax  is  decreased  in  size  the  reverse  of  the  above 
pressure  relation  exists,  and  the  air  is  expelled.  In  fact,  the  thorax  and  the 
lungs  behave  as  a  pair  of  bellows — just  as  air  is  drawn  into  the  expanding 
bellows,  so  is  air  drawn  into  the  lungs  by  the  enlargement  of  the  thorax  ; 
similarly,  as  the  air  is  forced  from  the  bellows  by  compression,  so  is  air 
forced  from  the  lungs  by  the  shrinkage  of  the  lungs  and   the  thorax. 

During  the  expansion  of  the  thorax  the  lungs  are  entirely  passive,  and  by 
virtue  of  their  perfect  elasticity  merely  follow  the  thoracic  walls,  from  which 
they  are  separated  only  by  the  two  layers  of  the  pleura?,  which,  being  moist- 
ened with  lymph,  slide  over  each  other  without  appreciable  friction.  That 
1  Virchow's  Archiv,  1891,  Bd.  126,  8.  523. 


AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

tlif  lungs  are  entirely  passive  is  shown  by  the  fact  that  when  the  thorax  is 
punctured,  so  as  to  allow  a  tree  communication  with  the  atmosphere,  expan- 
sion of  the  chest  is  no  longer  followed  by  dilatation  of  the  lungs.  During  the 
shrinkage  of  the  thorax  the  clastic  reaction  of  the  lungs  plays  an  active  part. 

Respiration,  Inspiration,  and  Expiration. — Each  respiration  or  respiratory 
act  consists  of  an  inspiration  (enlargement  of  the  thorax  and  inflation  of  the 
lungs)  and  an  expiration  (shrinkage  of  the  thorax  and  the  lungs).  Accord- 
ing to  some  observers,  a  'pause  exists  after  expiration  {expiratory  pause),  but 
during  quiet  breathing  no  such  interval  can  be  detected.  A  pause  mav  be 
present  when  the  respirations  are  deep  and  infrequent.  Under  certain  abnor- 
mal circumstances  a  pause  may  exist  between  inspiration  and  expiration 
(inspiratory  pa  use). 

Inspiration  is  accomplished  by  the  contraction  of  certain  muscles  which  are 
designated  inspiratory  muscles.  Expiration  during  quiet  breathing  is  essen- 
tially a  passive  act,  but  during  forced  breathing  various  muscles  are  active; 
these  muscles  are  distinguished  as  expiratory  muscles. 

During  inspiration  the  thorax  is  enlarged  in  the  vertical,  transverse,  and 
antero-posterior  diameters.  During  quiet  breathing  the  vertical  diameter  is 
increased  by  the  descent  of  the  diaphragm,  and  during  deep  inspiration  it  is 
further  increased  by  the  backward  and  slightly  downward  movement  of  the 
floating  ribs,  and  by  the  extension  of  the  vertebral  column,  which  raises  the 
sternum  with  its  costal  cartilages  and  ribs.  The  transverse  diameter  is  in- 
creased by  the  elevation  and  eversion  (rotation  outward  and  upward)  of  the 
ribs.  The  antero-posterior  diameter  is  increased  by  the  upward  and  outward 
movement  of  the  sternum,  costal  cartilages,  and  ribs.  During  quiet  inspiration 
in  men  the  sternum  is  not  raised  to  a  higher  level,  but  the  low^er  end  is  rotated 
forward  and  upward.  It  is  only  during  deep  inspiration  in  men  and  in  quiet 
or  deep  inspiration  in  women  that  the  sternum  as  a  whole  is  elevated. 

The  movements  of  the  anterior  and  lateral  walls  constitute  costal  respira- 
tion, and  those  of  the  diaphragm  diaphragmatic  or,  as  it  is  sometimes  called, 
abdominal  respiration,  since  the  descent  of  the  diaphragm  causes  protrusion 
of  the  abdominal  walls.  Both  types  coexist  during  ordinary  respiratory  move- 
ments, but  one  may  be  more  prominent  than  the  other.  The  costal  type  is  well 
marked  in  women,  and  the  diaphragmatic  type  in  men.  These  peculiarities 
are  not,  however,  due  to  inherent  sexual  differences,  but  to  dress.  Young 
children  of  both  sexes  exhibit,  as  a  rule,  the  diaphragmatic  type,  and  it  is 
only  later,  and  owing  to  constricting  dress,  that  the  costal  type  is  developed 
in  the  female. 

The  chief  muscles  of  inspirit  ion  are  the  diaphragm,  the  quadrat!  lumborum, 
the  serrati  postici  inferiores,  the  scateni,  the  serrati  postici  superiores,  the  leva- 
tores  cost, i mm  lonai  <t  breves,  and  the  intercostales  externi  >t  intercartilaginei. 

Movements  of  the  Diaphragm. — The  diaphragm  is  attached  by  its  two 
crura  to  the  first  three  or  four  lumbar  vertebrae,  to  the  lower  six  or  seven  cos- 
tal cartilages  and  adjoining  parts  of  the  corresponding  ribs,  and  to  the  poste- 
rior surface  of  the  ensiform  appendix.     It  projects  into  the  thoracic  cavity  in 


RESPIRATION.  399 

the  form  of  a  flattened  dome,  the  highest  part  being  formed  by  the  central 
tendon.  The  tendon  consists  of  three  lobes  which  are  partially  separated  by 
depressions.  The  right  lobe,  or  largest,  is  the  highest  portion  and  lies  over 
the  liver ;  the  left  lobe,  which  is  the  smallest,  lies  over  the  stomach  and  the 
spleen ;  while  the  central  lobe  is  situated  anteriorly,  the  upper  surface  blending 
with  the  pericardium.  The  central  tendon  is  a  common  point  of  insertion 
of  all  the  muscular  fibres  of  the  diaphragm.  In  the  passive  condition  the 
lower  portions  of  the  diaphragm  are  in  apposition  to  the  thoracic  Malls. 
During  contraction  the  whole  dome  is  drawn  downward,  while  the  parts  of 
the  muscle  in  contact  with  the  chest  are  pulled  inward.  According  to  Hult- 
kranz,  the  cardiac  part  of  the  diaphragm  descends  from  5.5  to  11.5  millimeters 
during  quiet  inspiration,  and  as  much  as  42  millimeters  during  deep  inspira- 
tion. Not  only  is  the  height  of  the  arch  lessened,  but  there  is  also  a  tendency, 
owing  to  the  points  of  attachment  of  the  diaphragm,  toward  the  pulling  of  the 
lower  ribs  with  their  costal  cartilages  and  the  lower  end  of  the  sternum  inward 
and  upward ;  this  traction,  however,  is  counterbalanced  by  the  pressure  of  the 
abdominal  viscera,  the  latter  being  forced  downward  and  outward  against  the 
thoracic  and  abdominal  walls.  If  this  counterbalancing  pressure  be  removed 
by  freely  opening  the  abdominal  cavity,  especially  after  removing  the  viscera, 
the  lower  lateral  portions  of  the  thorax  will  be  seen  during  each  inspiration  to 
be  drawn  inward.  It  is  during  labored  inspiration  only  that  this  movement 
occurs  in  the  intact  individual. 

When  the  diaphragm  ceases  to  contract,  the  elastic  recoil  of  the  distended 
lungs  is  sufficient  to  draw  the  sunken  dome  upward  into  the  passive  position. 
This  upward  movement  of  the  diaphragm  is  aided  by  the  positive  intra- 
abdominal pressure  exerted  by  the  elastic  tension  of  the  abdominal  walls 
through  the  medium  of  the  abdominal  viscera.  In  forced  expiration  the 
contraction  of  the  abdominal   muscles  (p.  407)  adds  additional  force. 

The  quadrati  lumborum  are  believed  to  assist  the  diaphragm  by  fixing  the 
twelfth  ribs,  or  even  lowering  and  drawing  them  backward  duringdeep  inspira- 
tion. Each  of  these  muscles  arises  from  the  ilio-lumbar  ligament  and  the  iliac- 
crest,  and  is  inserted  into  the  transverse  processes  of  the  first,  second,  third,  and 
fourth  lumbar  vertebrae  and  the  lower  border  of  one-half  of  the  length  of  the 
last  rib.   These  muscles  are  regarded  by  some  physiologists  as  expiratory  agents. 

The  serrati  postici  inferloj-es  similarly  assist  the  diaphragm  by  drawing  the 
lower  four  ribs  backward,  and  in  deep  inspiration  also  downward.  They  not 
only  thus  oppose  the  tendency  of  the  diaphragm  to  pull  the  lower  ribs 
upward  and  forward,  which  would  lessen  its  effectiveness  in  enlarging  the 
vertical  diameter  of  the  thorax,  but  they  contribute  to  this  enlargement  by 
their  backward  and  downward  traction  upon  the  rib-  and  the  attached  por- 
tions of  the  diaphragm.  These  muscles  pass  from  the  spines  of  the  eleventh 
ami  twelfth  dorsal  and  first  two  or  three  lumbar  vertebrae  and  the  supraspi- 
nous ligament  to  the  lower  borders  of  the  ninth,  tenth,  eleventh,  and  twelfth 
ribs,  beyond  their  angles. 

Simultaneously  with   the   contraction  of  the  diaphragm  the   thoracic  walls 


400 


AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 


are  drawn  upward  and  outward  by  the  contractions  of  other  inspiratory  mus- 
cles, thus  enlarging  the  thorax  in  the  antero-posterior  and  lateral  diameters. 

Movements  of  the  Ribs. — The  movements  of  the  ribs  during  inspiration 
arc,  as  a  whole,  essentially  rotations  upward  and  outward  upon  axes  which  are 
directed  obliquely  outward  and  backward,  each  axis  being  directed  through 
the  costo-vertebral  articulation  and  a  little  anterior  to  the  costotransverse 
articulation.  The  vertebral  ends  of  the  ribs  lie  higher  than  their  sternal 
extremities,  so  that  when  the  ribs  are  elevated  the  anterior  ends  are  advanced 
forward  and  upward.  The  arches  of  the  ribs  are  inclined  downward  and 
outward,  and,  owing  to  the  obliquity  of  the  axes  of  rotation,  the  convexities 
are  rotated  upward  and  outward,  or  everted.  Thus  both  the  antero-posterior 
and  lateral  diameters  are  increased. 

The  degree  of  obliquity  of  the  axes  of  rotation  of  the  different  ribs  varies. 
The  axis  of  the  first  rib  is  almost  transverse  (Fig.  69),  while  that  of  each 
succeeding  rib  to  the  ninth,  inclusive,  becomes  more  oblique  (Fig.  70).     The 


Fig.  69.— First  dorsal  vertebra  and  rib. 


Fig.  70.— Sixth  dorsal  vertebra  and  rib. 


more  oblique  the  axis,  the  greater  the  degree  of  eversion ;  consequently  the 
first  rib  is  capable  of  but  .-light  eversion,  while  the  lower  ribs  may  be  everted 
to  a  relatively  marked  extent.  Moreover,  the  peculiarities  or  the  absence  of 
the  costo-transverse  articulations  materially  affect  the  character  of  the  move- 
ments of  the  differenl  ribs.  Thus,  the  facets  on  the  transverse  processes  of  the 
first  and  second  dorsal  vertebrae  are  cup-shaped,  and  into  them  are  inserted 
the  conical  tuberosities  of  the  ribs,  thus  materially  limiting  the  rotation  of  the 
ribs;  while  the  facets  for  the  articulations  of  the  third  to  the  tenth  ribs,  inclu- 
sive, assume  a  plane  character  which  admits  of  larger  movement.  The  facets 
for  the  third  to  the  fifth  ribs  are  almost  vertical,  thus  allowing  a  free  move- 
ment upon  the  oblique  axis;  while  the  facets  for  the  sixth  to  the  ninth  ribs, 
inclusive,  are  directed  obliquely  upward  and  backward,  and  admit  of  a  move- 


RESPIRA  TION.  40 1 

ment  upward  and  backward  as  well  as  a  rotation  upon  the  oblique  axis. 
Finally,  the  eleventh  and  twelfth  ribs  (and  generally  the  tenth)  have  no  costo- 
transverse articulations,  allowing  a  movement  backward  and  forward  as  well 
as  rotation  upon  their  oblique  axes.  While,  therefore,  the  movements  of  the 
ribs  are  essentially  rotations  upward,  forward,  and  outward  upon  oblique  axes 
directed  through  the  eosto-vertebral  articulations  and  a  little  anterior  to  the 
costo-trans verse  articulation,  they  are  more  or  less  modified  by  reason  of  the 
motion  permitted  by  the  nature  or  the  absence  of  the  costo-transverse  articu- 
lations. Thus,  the  essential  character  of  the  movement  of  the  first  to  the 
fifth  ribs  is  a  rotation  upward,  forward,  and  outward ;  that  of  the  sixth  to 
the  ninth  ribs,  a  rotation  upward,  forward,  and  outward  combined  with  a 
movement  upward  and  backward;  that  of  the  tenth  and  eleventh  ribs,  a 
rotation  upward,  forward,  and  outward  with  a  rotation  backward  ;  that  of 
the  twelfth  rib,  chiefly  a  rotation  backward  and  rather  downward.  The 
character  of  the  movement  of  each  rib  differs  somewhat  as  we  pass  from 
the  first  to  the  twelfth  ribs. 

During  forced  inspiration  the  sternum  and  its  attached  costal  cartilages 
with  their  ribs  are  pulled  upward  and  outward,  while  the  ninth,  tenth, 
eleventh,  and  twelfth  ribs  are  drawn  backward  and  downward.  During 
expiration  these  movements  are  of  course  reversed. 

The  intercostal  spaces  during  inspiration,  except  the  first  two,  are  widened.1 
The  reason  for  this  opening  out  must  be  apparent  when  we  remember  that 
the  ribs  are  arranged  in  the  form  of  a  series  of  parallel  curved  bars  directed 
obliquely  downward,  and  the  fact  may  be  demonstrated  by  means  of  a  very  sim- 
ple model  (Fig.  71)  consisting  of  a  vertical  support  and  two  parallel  bar-,  a,  b, 
placed  obliquely.  If,  after  measuring  the  distance  c,  d,  we 
raise  the  bars  to  a  horizontal  position,  the  distance  c,J  will 
be  found  to  be  greater  than  c,  d,  since  the  bars  rotate  around 
fixed  points  placed  in  the  same  vertical  line.  This  widening 
of  the  intercostal  spaces  is  readily  accomplished  because  of 
the  elasticity  of  the  costal  cartilages. 

The  muscles  which  may  be  involved  in  the  movements 
of  the  ribs  during  quiet  inspiration  include  the  scaleni,  the 
serrati  postid  superiores,  the  levatores  eostarum  longiet  breves, 
and  the  intercostales  externi  ei  intercartilaginei. 

The  Hcaleni  are  active  in  fixing  the  first  and  second  ribs,  iustrat<   the  widening 

thus  <■stal.lisl.ing,  as  it  were,  a  firm   basis  from  which   the  ';r,h"i","r' :.08a^1ftsnpace9 
~'  during  Inspiration. 

external  intercostal  muscles  may  act.  The  scalenus  anticus 
pusses  between  the  tubercles  of  the  transverse  processes  of  the  third,  fourth, 
fifth,  and  sixth  cervical  vertebrae  to  the  scalene  tubercle  on  the  firsl  rib. 
The  scalenus  medius  passes  from  the  posterior  tubercles  of  the  transverse 
processes  of  the  lower  six  cervical  vertebra1  to  the  upper  surface  of  the 
first  rib,  extending  from  the  tubercle  to  just  behind  the  groove  for  the 
subclavian  artery.     The    scalenus    posticus   passes    from    the    transverse   pro- 

1  Elmer:  Arehivjur  Anatomie  vmd  Physiologic,  Anatomiscbe  Abtheilung,  L886,  8.  L99. 
Vol.  I.— 2fi 


11.    Model  to  [1- 


402  AN    AMERICAN   TEXT- BO  OK   OF  PHYSIOLOGY. 

cesses  of  the  two  or  three  lower  cervical  vertebrae  to  the  outer  surface  of  the 
second  rib. 

The  serrati  postid  mperiorea  aid  in  fixing  the  second  ribs  and  raise  the  third, 
fourth,  and  fifth  ribs.  The  muscles  )>a>s  from  the  ligamentum  nuchae  and  the 
spines  of  theseventh  cervical  and  first  two  or  three  dorsal  vertebrae  to  the  upper 
borders  of  the  second,  third,  fourth,  and  fifth  ribs,  beyond  their  angles. 

The  levatores  costarum  breves  consist  of  twelve  pairs  which  pass  from  the 
tips  of  the  transverse  processes  of  the  seventh  cervical  and  first  to  the  eleventh 
dorsal  vertebrae  downward  and  outward,  each  being  inserted  between  the 
tubercle  and  the  angle  of  the  next  rib  below.  Those  arising  from  the  lower 
ribs  send  fibres  to  the  second  vertebra  below  [levatores  costarum  longiores). 
They  assist  in  the  elevation  and  eversion  of  the  first  to  the  tenth  ribs,  inclusive, 
and  co-operate  with  the  quadrati  lumborum  and  the  serrati  postici  inferiores 
to  draw  the  lower  ribs  backward. 

The  functions  of  the  intercostales  have  been  a  matter  of  dispute  for  centu- 
ries, and  the  problem  is  still  unsettled.  For  instance,  Galen  looked  upon  the 
external  intercostals  as  being  expiratory.  Vesalius  asserted  that  both  the 
external  and  the  internal  intercostals  are  expiratory,  while  Haller  expressed 
the  opposite  belief.  Hamberger  and  Hutchinson  regarded  the  external  inter- 
costals and  the  intcrchondrals  as  being  inspiratory,  and  the  interosseous  portion 
of  the  internal  intercostals  as  being  expiratory.  Finally,  Landois  believes  that 
while  the  external  intercostals  and  the  intcrchondrals  are  active  during  inspira- 
tion, and  the  interosseous  portion  of  the  internal  intercostals  during  expiration, 
their  chief  actions  are  not  to  enlarge  nor  to  diminish  the  volume  of  the  thoracic 
cavity,  but  to  maintain  a  proper  degree  of  tension  of  the  intercostal  spaces. 
Each   view  still  has  its  adherents. 

The  actions  of  the  intercostal  muscles  are  generally  demonstrated  by  means 
of  rods  and  clastic  bands  arranged  in  imitation  of  the  ribs  and  the  origins  and 
insertions  of  the  muscles,  or  by  geometric  diagrams.  The  well-known  model 
of  Bernouilli  consists  of  a  vertical  bar  representing  the  vertebral  column,  upon 
which  bar  move  two  parallel  straight  rods  in  imitation  of  the  ribs  (Fig.  72). 
If  the  rods  be  placed  at  an  oblique  angle  and  a  tense  rubber  band  (a,  b)  be 
affixed  to  represent  the  relations  of  the  external  intercostals,  the  rods  will  be 
pulled  upward  and  the  space  between  them  will  be  widened.  The  interchon- 
dral  portion  of  the  internal  intercostal-  bears  the  same  oblique  relation  to  the 
costal  cartilages,  and  theoretically  should  have  the  same  action.  The  action 
of  the  interosseous  portion  of  the  internal  intercostals  is  demonstrated  in  this 
way:  If  the  rubber  band  be  placed  at  right  angles  to  the  rods  (Fig.  73,  a,  b) 
and  the  rods  be  raised  to  a  horizontal  position,  the  rubber  is  put  on  the  stretch 
(c,  d),  so  that  when  the  rods  are  released  they  will  be  pulled  downward  by  the 
elastic  reaction  of  the  rubber.  This  last  demonstration  has  been  held  to  indi- 
cate that  during  inspiration  the  interosseous  portion  of  the  internal  intercostals 
i-  put  on  the  stretch  and  in  an  oblique  position,  and  therefore  in  a  relation 
favorable  tor  effective  action  during  contraction.  The  ribs,  however,  differ 
essential Iv  from  such  a  model  in  the  fact  that  they  are  curved  bars,  that  their 


RESPIRATJOX. 


403 


ends  are  not  free,  and  that  the  movement  of  rotation  is  materially  different. 
In  fact,  the  mechanical  conditions  are  so  complex  that  deductions  from  phe- 
nomena observed  in  such  gross  demonstrations  or  by  means  of  geometric  figures 
such  as  suggested  by  Rosenthal  and  others  must  be  accepted  with  caution. 

There  is  no  doubt  that  stimulation  of  any  of  the  intercostal  fibres  causes 
an  elevation  of  the  rib  below  if  the  rib  above  be  fixed,  and  that  if  the  excita- 
tion be  sufficiently  strong  and  the  area  be  large,  the  effect  may  extend  from  rib 
to  rib,  and  thus  a  large  part  of  the  thoracic  cage  will  be  elevated.  Conse- 
quently, it  has  been  assumed  that,  should  the  upper  ribs  be  fixed,  the  contrac- 
tions of  both  sets  of  intercostals  would  elevate  the  system  of  ribs  below.  But 
the  experiments  of  Martin  and  Hartwell l  show  that  during  forced  inspiration 
the  internal  intercostals  contract  alternately  with  the  diaphragm  and  the  exter- 
nal intercostals,  and  therefore  are  expiratory.  Moreover,  Ebner2  has  found, 
as  a  result  of  elaborate  measurements,  that  the  intercostal  spaces,  excepting  the 
first  two,  are,  instead  of  being  narrowed,  actually  widened  during  inspiration. 


Fig.  72. — Model  to  illustrate  the  action  of  the 
external  intercostals  and  interchondrals. 


Fig.  73.— Model  to  illustrate  the  action  of  the  inter- 
osseous portion  of  the  internal  intercostals. 


An  examination  of  the  origins  and  insertions  of  the  external  intercostals  and 
the  interosseous  portion  of  the  internal  intercostals,  and  of  their  actions  during 
contraction,  renders  it  apparent  that  it  is  possible  for  the  externi  to  elevate  the 
ribs  and  to  widen  the  intercostal  spaces,  but  that  such  effects  are  impossible  in 
the  case  of  the  interosseous  portion  of  the  internal  intercostals.  Thus,  if  we 
take  the  model  described  above  (Fig.  72),  project  a  line  a,  6  in  imitation  of 
the  relation  of  the  external  intercostals  to  the  ribs,  and  raise  the  parallel  bars 
to  a  horizontal  position,  the  distance  between  c,  d  is  shorter  than  that  between 
a,  l>.  It  is  but  a  logical  step  from  this  demonstration  to  assume  that,  should  a 
strip  of  muscle  be  placed  between  «,  b,  the  muscle  in  shortening  would  pull  the 
bars  upward,  at  the  same  time  widening  the  intercostal  spaces.  1 1"  now  the 
upper  ribs  be  fixed,  it  is  obvious  that  the  external  intercostals  must  raise  the 
ribs  and  open  up  the  intercostal  spaces  during  contraction.  This  same  reason- 
ing applies  to  the  interchondrals,  and  the  experiments  of  Hough3  show  that 
they  contract  synchronously  with  the  diaphragm,  and  therefore  with  the  exter- 
nal intercostals. 

1  Journal  of  Physiology,  1S79-80,  vol.  2,  p.  24.  2  Lnr.  ril. 

3  Studies  from  the  Biological  Laboratory,  Johns  Hopkins  University)  March,  1894. 


404  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

In  considering  the  interosseous  portion  of  the  internal  intercostals  we  find 
that  during  the  passive  condition  they  are  placed  nearly  at  right  angles  to  the 
ribs.  H'  contraction  takes  place,  it  is  obvious  that  the  mechanical  response 
must  be  an  approximation  of  the  ribs  and  a  lessening  of  the  width  of  the  inter- 
costal spaces.  It  must  also  be  apparent  that  during  the  movement  of  inspira- 
tion these  fibres  are  put  on  the  stretch,  which  can  be  demonstrated  in  the  above 
model.  Thus,  if  we  put  a  rubber  band  at  right  angles  to  the  parallel  rods 
(Fig.  73),  we  will  find  that  when  the  rods  are  in  the  horizontal  position,  in 
imitation  of  the  position  of  the  ribs  at  the  beginning  of  expiration,  the  distance 
between  c,  '/  is  greater  than  that  between  a,  b ;  therefore  if  we  lessen  the  dis- 
tance between  e,  r/,  as  when  the  muscle-fibres  contract,  the  mechanical  result  of 
contraction  must  be  approximation,  the  opposite  to  that  which  occurs  during 
inspiration. 

While  the  whole  subject  of  the  actions  of  the  intercostal  muscles  must  still 
be  regarded  as  in  an  unsettled  condition,  yet  there  is  no  reasonable  doubt  that 
the  externi  and  the  intercartilaginei  contract  during  inspiration,  and  the  inter- 
osseous portion  of  the  internal  intercostals  during  expiration.  Admitting  this 
to  be  true,  it  is,  however,  by  no  means  clear  whether  or  not  these  muscles  are 
for  the  purpose  of  altering  the  volume  of  the  thorax.  It  is  probable,  as  sug- 
gested by  Landois,  that  their  chief  function  is  to  maintain,  during  all  phases 
of  the  respiratory  movements,  a  proper  degree  of  tension  of  the  intercostal 
tissues.  If  this  view  be  correct,  the  external  intercostals  and  interchondrals  con- 
tract during  inspiration  chiefly  for  the  purpose  of  causing  greater  tension  of 
the  intercostal  tissues,  so  as  to  counteract  the  influence  of  the  increase  of 
negative  intrathoracic  pressure ;  while  during  expiration,  when  their  relax- 
ation occurs,  a  substitution  for  this  relaxation  is  provided  by  the  contraction 
of  the  interosseous  portion  of  the  internal  intercostals,  so  that  the  tension  of 
the  intercostal  tissues  is  maintained.  The  internal  intercostals  must  prove 
most  effective  during  forced  expiratory  efforts — for  example,  in  coughing, 
when  the  intercostal  tissues  are  subjected  to  high  positive  intrathoracic  pres- 
sure, and  there  is  a  consequent  tendency  to  outward  displacement,  which  is 
met  and  counteracted   by  the   internal   intercostals. 

During  forced  inspiration  the  scaleni  and  the  serrall  j>ostiel  superiores  con- 
tract vigorously,  so  that  the  sternum  and  the  first  five  ribs  are  elevated,  thus 
raising  the  thoracic  cage  as  a  whole.  At  the  same  time  the  serrati  postid 
inferiores,  the  quadraii  lumborum,  and  the  sacro-lumbaies  are  active  in  pulling 
the  lower  ribs  downward  and  backward.  Besides  these  muscles  there  are  a 
number  of  others  which  directly  or  indirectly  affect  the  size  of  the  thorax  and 
which  may  be  brought  into  activity  ;  chief  among  these  are  the  slerno-chi<l<>- 
mastoidei,  the  trapezei,  the  pectorales  minores,  the  perforates  majores  (costal 
portion),  the  rhomboidei,  and  the  erectores  s/)ince. 

The  xfenio-cteido-mastoid  passes  from  the  mastoid  process  and  the  superior 
curved  line  of  the  occipital  bone  to  the  upper  front  surface  of  the  manubrium 
and  the  upper  bolder  of  the  inner  third  of  the  clavicle.  These  muscles  ele- 
vate  the   upper  part  of  the  chest  when   the   head   and    neck   are  fixed.     The 


RESPIRA  TIOX.  405 

trapezius  passes  from  the  occipital  bone,  the  ligamentum  nucha?,  the  spines  of 
the  seventh  cervical  and  of  all  the  dorsal  vertebra,  and  the  supraspinous  liga- 
ment to  the  posterior  border  of  the  outer  third  of  the  clavicle,  the  inner  border 
of  the  acromion  process,  the  crest  of  the  spine  of  the  scapula,  and  to  the 
tubercle  near  the  root.  The  trapezei  help  to  fix  the  shoulders.  The  rhomboid- 
eus  minor  passes  from  the  ligamentum  nucha?  and  the  spines  of  the  seventh 
cervical  and  first  dorsal  vertebrae  to  the  root  of  the  spine  of  the  scapula.  The 
rhomboideus  major  passes  from  the  spines  of  the  first  four  or  five  dorsal  vertebrae 
and  the  supraspinous  ligament  to  the  inferior  angle  of  the  scapula.  The  trapezei 
and  rhomboidei  fix  the  shoulders,  affording  a  base  of  action  from  which  the 
pectorales  act.  The  pectoralis  major  passes  from  the  pectoral  ridge  of  the 
humerus  to  the  inner  half  of  the  anterior  surface  of  the  clavicle,  the  corre- 
sponding half  of  the  anterior  surface  of  the  sternum,  the  cartilages  of  the 
first  six  ribs,  and  the  aponeurosis  of  the  external  oblique  muscle.  The  pecto- 
ralis minor  passes  from  the  coracoid  process  of  the  scapula  to  the  upper  margin 
and  outer  surface  of  the  third,  fourth,  and  fifth  ribs  close  to  the  cartilages  and 
to  the  intercostal  aponeuroses.  The  pectorales  minores  and  the  costal  portion 
of  the  pectorales  majores  raise  the  ribs  when  the  shoulders  are  fixed.  The 
erectorcs  spina?  are  composite  muscles  extending  along  each  side  of  the  spinal 
column,  each  consisting  of  the  sacro-lumbalis,  the  musculus  accessorius,  the 
cervicalis  ascendens,  the  longissimus  dorsi,  the  transversalis  cervicis,  the  trachelo- 
mastoid,  and  the  spinalis  dorsi.  The  erectores  spinae  straighten  and  extend  the 
spine  and  the  neck,  and  thus  tend  to  raise  the  sternum,  the  costal  cartilages, 
and  the  ribs.  The  infrahyoidei  may  also  be  included  among  the  muscles 
engaged  in  forced  inspiration,  since  they  may  aid  in  the  elevation  of  the  sternum. 

Summary  of  the  Actions  of  the  Chief  Muscles  of  Inspiration. — Dur- 
ing quiet  inspiration  the  diaphragm  contracts,  thus  increasing  the  vertical  diam- 
eter of  the  thorax,  its  effectiveness  being  augmented  by  the  associated  actions 
of  the  quadrati  lumborum  and  the  serrati  postici  inferiores,  the  tinnier  fixing 
the  twelfth  ribs,  and  the  latter  fixing  the  ninth,  tenth,  eleventh,  and  twelfth 
ribs,  and  thus  preventing  the  muscular  slips  of  the  diaphragm  attached  to  these 
ribs  from  drawing  them  inward  and  upward  and  thus  diminishing  the  cavity 
of  the  thorax.  Coincidcntly  with  the  contractions  of  these  muscles  the  seal  ni 
fix  the  first  and  second  ribs,  and  the  serraU  postici  superiores  aid  in  fixing  the 
second  ribs  and  elevate  the  third,  fourth,  and  fifth  ribs  ;  the  intercostales  extemi 
et  intercartilaghiei  and  the  levatores  costarum  tongi  >  I  bn  ves  elevate  and  evert  the 
first  to  the  tenth  ribs,  inclusive,  throwing  the  lower  end  of  the  sternum  for- 
ward; and  the  levatorcs,  in  conjunction  with  the  quadrati  lumborum  and  the 
8t ■rrati postici  inferiores,  aid  in  fixing  the  lower  ribs  and  even  draw  them  buck- 
ward.  The  intercostales  extern/  also  serve  to  maintain  a  proper  degree  of  tension 
of  the  intercostal  tissues. 

During  forced  inspiration  the  scaieni  and  the  serrati  postici  superiores  act 
more  powerfully  and  thus  raise  the  sternum  with  its  attached  costal  cartilages 
and  ribs,  being  assisted  by  the  sterno-cleido-Tnastoidei  and  the  infrahyoidei 
when  the  head  and  neck  are  fixed,  and  by  the  pectorales  majores  et  minores 


406  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

when  the  shouldersare  fixed  by  thetrapezei  and  the  rhomboidei.     The  erectores 
spina-  further  assist  this  action   by  extending  the  spinal  column. 

Movements  of  Expiration. — During  quiet  breathing;  expiration  is  effected 
mainly  or  solely  by  the  passive  return  of  the  displaced  parts.  Normal  expi- 
ration is  therefore  essentially  a  passive  act,  although  it  may  be  assisted  by  the 
contraction  of  the  interosseous  portion  of  the  internal  intercostals.  The  most 
important  factors  are  unquestionably  the  elastic  tension  of  the  lungs,  costal 
cartilages,  intercostal  spaces,  and  abdominal  walls,  together  with  the  weight  of 
the  chest. 

The  lungs  after  quiet  expiration  are  in  a  state  of  elastic  tension  equal  to  a 
pressure  of  +1.9  to  +3.9  millimeters  of  mercury  (see  p.  397),  which  pressure 
during  inspiration  is  increased  in  proportion  to  the  depth  of  the  movement. 
As  soon,  therefore,  as  the  inspiratory  muscles  cease  to  contract,  this  tension 
comes  into  play,  and,  aided  by  elastic  and  mechanical  reactions  below  noted, 
forces  air  from  the  lungs.  This  elasticity,  and  the  facility  with  which  the  air 
is  expelled,  may  be  demonstrated  by  inflating  a  pair  of  excised  lungs  and  then 
suddenly  allowing  a  free  egress  of  the  air :  collapse  occurs  with  remarkable 
rapidity,  with  a  force  proportionate  to  the  degree  of  distention.  The  elastic 
costal  cartilages  are  similarly  put  on  the  stretch  :  the  lower  borders  are  drawn 
outward  and  upward  and  are  thus  twisted  out  of  position,  so  that  as  soon  as 
the  inspiratory  forces  are  withdrawn  they  must  untwist  themselves,  further 
aiding  the  elastic  reaction  of  the  lungs.  The  intercostal  spaces,  excepting  the 
first  two,  are  widened  and  the  tissues  are  stretched,  and  the  diaphragm  during 
its  descent  presses  upon  the  abdominal  viscera,  rendering  the  abdominal  walls 
tense.  When,  therefore,  inspiration  ceases  the  reaction  of  the  tense  and  elastic 
intercostal  tissues  aids  in  bringing  the  chest  into  the  position  of  rest,  while  the 
stretched  abdominal  walls  press  upon  the  abdominal  viscera  and  thus  force 
the  diaphragm  upward.  Finally,  the  chest-walls  by  their  weight  tend  to  fall 
from  the  position  to  which  they  have  been  raised,  adding  thus  another  factor 
toward  the  elastic  reaction  of  the  lungs,  costal  cartilages,  intercostal  tissues,  and 
abdominal  walls. 

Whether  or  not  the  interosseous  portion  of  the  internal  intercostal  muscles 
assists  in  expiration  cannot  be  stated  with  positiveness.  The  fact  that  these 
muscles  contract  during  the  expiratory  phase  and  that  the  contraction  results 
in  an  approximation  of  the  ribs  leads  to  the  belief  that  they  are  expiratory., 
lint,  as  before  stated  (p.  1»>1),  this  activity  may  be  primarily  for  the  purpose 
of  maintaining  a  proper  degree  of  tension  of  the  intercostal  tissues.  In  the 
doe-  these  muscles  are  not  active  until  dyspnoea  appears,  while  in  the  cat  they 
do  not  come  into  play  until  extreme  dyspnoea  has  set  in  (Martin  and  Hartwell). 
These  facts  certainly  militate  against  regarding  them  as  active  expiratory  fac- 
tors during  quiel  breathing,  while  during  forced  expiration  they  may  with 
accuracy  be  considered  as  being  in  part  at  leas!  expiratory  in  function.  We  are 
therefore  justified  in  concluding  thai  normal  quiet  expiration  is  essentially  a 
passive  act  due  to  elastic  reaction  and  to  the  mechanical  replacement  of  dis- 
placed parts. 


RESPIRATION.  407 

During  forced  expiration  certain  muscles  may  be  active,  the  chief  being  the 
intercostales  intend  interossei,  the  triangulares  sterni,  the  museuli  abdominales, 
and  the  levatores  ami.  The  intercostales  intend  interossei  are  probably  active 
expiratory  muscles  during  forced  expiration,  but  they  can  prove  effective  only 
when  the  lower  part  of  the  thoracic  cage  is  fixed  or  drawn  down — an  act  which 
is  accomplished  chiefly  by  the  abdominal  muscles. 

The  triangulares  sterni  pass  outward  and  upward  from  the  lower  part  of 
the  sternum,  the  inner  surface  of  the  ensiform  cartilage,  and  the  sternal 
ends  of  the  costal  cartilages  of  the  two  or  three  lower  sternal  ribs,  to  the  lower 
and  inner  surfaces  of  the  cartilages  of  the  second  to  the  sixth  ribs,  inclusive. 
They  draw  the  attached  costal  cartilages  downward  during  expiration. 

The  abdominales  during  quiet  expiration  are  passive,  and  aid  in  the  expul- 
sion of  air  from  the  lungs  simply  by  their  elasticity  ;  but  during  forced  expi- 
ration, by  contraction,  they  are  active  expiratory  factors. 

The  obliquus  externus  arises  by  slips  on  the  outer  surface  and  lower  borders 
of  the  lower  eight  ribs,  and  is  inserted  into  the  outer  lip  of  the  anterior  half 
of  the  crest  of  the  ilium  and  into  the  broad  aponeurosis  which  blends  with 
that  of  the  opposite  side  in  the  linea  alba.  The  obliquus  internus  passes 
from  the  outer  half  or  two-thirds  of  Poupart's  ligament,  the  anterior  two-thirds 
of  the  middle  lip  of  the  crest  of  the  ilium,  and  the  posterior  layer  of  the  lumbar 
fascia  to  the  cartilages  of  the  last  three  ribs  and  the  aponeurosis  of  the  anterior 
part  of  the  abdominal  wall.  The  rectus  abdominis  passes  from  the  crest  of  the 
pubes  and  the  ligaments  in  front  of  the  symphysis  pubis  to  the  cartilages  of 
the  fifth,  sixth,  and  seventh  ribs,  and  usually  to  the  bone  of  the  fifth  rib.  The 
transversalis  abdominis  passes  from  the  outer  third  of  Poupart's  ligament,  the 
anterior  three-fourths  of  the  inner  lip  of  the  iliac  crest,  by  an  aponeurosis 
from  the  transverse  and  spinous  processes  of  the  lumbar  vertebrae,  and  from 
the  inner  surface  of  the  sixth  lower  costal  cartilages  to  the  pubic  crest  and  the 
linea  alba.  The  fibres  for  the  most  part  have  a  horizontal  directi<  >n.  The  pyram- 
idcdls  passes  from  the  anterior  surface  of  the  pubes  and  the  pubic  ligament 
to  the  linea  alba.  It  is  obvious  from  the  points  of  origin  and  insertion  of  the 
abdominal  muscles  that  during  contraction  they  co-operate  toward  diminishing 
the  volume  of  the  thorax  in  three  ways:  (1)  By  offering  a  base  of  action  for 
the  internal  intercostals,  and  thus  aiding  in  the  approximation  of  the  ribs; 
(2)  by  depressing  and  drawing  inward  the  lower  end  of  the  sternum  and  the 
lower  costal  cartilages  and  ribs;  (3)  by  forcing  the  abdominal  viscera  against 
the  diaphragm,  thrusting  it  upward.  The  abdominales  are  unquestionably 
the  chief  expiratory   muscles. 

The  levatores  ani  converge  from  the  pelvic  wall  to  t ho  inner  part  of  the  rec- 
tum and  the  prostate  gland.  They  form  the  largest  part  of  the  muscular  floor 
of  the  pelvic  cavity.  The  levatores  ani  are  important  during  forcible  expi- 
ration by  resisting  the  downward  pressure  of  the  pelvic  viscera  caused  by  the 
powerful  contractions  of  the  abdominal  muscles,  but  they  must  be  regarded  rather 
as  associated  in  the  act  of  expiration,  and  not  as  true  expiratory  muscles. 

Summary  of  the  Actions  of  the  Chief  Muscles  of  Expiration. — During 


408  AN  AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

quiet  expiration  no  muscular  factors  are  involved,  unless  it  be  the  contraction 
of  the  intercostales  intemi  interossei,  in  which  event  they  are  more  probably 
engaged  in  maintaining  the  tension  of  the  intercostal  tissues  than  in  actually 
diminishing  the  capacity  of  the  thorax. 

During/orced  expiration  the  abdominales  flex  the  thorax  upon  the  pelvis, 
force  the  abdominal  viscera  against  the  diaphragm,  thrusting  it  upward,  and 
by  pulling  upon  the  lower  margins  of  the  thoracic  cage  draw  them  inward 
and  at  the  same  time  offer  a  base  from  which  the  intercostales  intemi  inter- 
ossei act  to  pull  the  ribs  downward;  the  triangulares  stemi  contract  at  the 
same  time  and  pull  downward  the  cartilages  of  the  second  to  the  sixth  ribs, 
inclusive. 

Associated  Respiratory  Movements. — Associated  with  the  thoracic  and 
abdominal  movements  of  respiration  are  movements  of  the  face,  pharynx,  and 
larynx.  The  nostrils  arc  slightly  dilated  during  inspiration  and  passively 
return  to  their  condition  of  rest  during  expiration  ;  the  soft  palate  moves  to 
and  fro  with  the  inflow  and  outflow  of  air,  and  the  glottis  is  widened  during 
inspiration  and  narrowed  during  expiration.  During  labored  inspiration, 
besides  the  above  movements,  the  mouth  is  usually  opened;  the  muscles  con- 
cerned in  facial  expression  may  be  active,  giving  the  individual  an  appearance 
of  distress;  the  soft  palate  is  raised,  and  the  larynx  descends.  The  widening 
of  the  nares  and  the  glottis,  the  opening  of  the  mouth,  the  elevation  of  the  soft 
palate,  and  the  descent  of  the  larynx  during  inspiration  are  obviously  for  the 
purpose  of  lessening  the  resistance  to  the  inflow  of  air. 

Intrapulmonary  or  Respiratory  Pressure  and  Intrathoracic  Pressure. 
— The  tidal  flow  of  air  to  and  from  the  lungs  during  the  respiratory  move- 
ments is  due,  as  already  stated,  to  the  differences  between  the  pressure  within 
the  lungs  and  that  outside  the  body.  During  inspiration  the  enlargement  of 
the  thorax  causes  an  expansion  of  the  lungs  and  a  consequent  diminution  of 
pressure  within  them,  so  the  air  is  forced  through  the  air-passages  until  the 
pressure  within  the  lungs  equals  that  of  the  atmosphere;  during  expiration 
there  occur  elastic  and  mechanical  reactions  whereby  the  pressure  within  the 
lungs  is  greater  than  that  of  the  atmosphere,  consequently  air  is  expelled  until 
an  equilibrium  is  again  established.  It  is  apparent,  then,  that  during  inspira- 
tion there  exists  within  the  lungs  a  condition  of  negative  pressure,  and  that 
during  expiration  the  pressure  is  positive.  If  a  manometer  be  so  arranged  as 
in  do  way  to  interfere  with  the  ingress  and  egress  of  air,  it  will  be  found  that 
during  inspiration  the  column  of  mercury  sinks,  while  during  expiration  it 
rises.  Donders  found  by  connecting  a  manometer  with  the  nasal  passage  that 
the  pressure  during  quiet  inspiration  was  — 1  millimeter  of  ITg,  and  during 
expiration  +2  to  3  millimeters.  Ewald  gives  as  corresponding  values — 0.1 
millimeter  and  -f-0.13  millimeter,  and  Mundhorst,  — 0.5  millimeter  and  +5 
millimeters.  During  deep  inspiration  Donders  noted  a  pressure  of — 30  milli- 
meter-, and  when  the  mouth  and  nose  were  closed,  — 57  millimeters.  During 
forced  expiration,  with  respiratory  passage  closed,  it  was  +87  millimeters;  but 
these  figures  have  been  exceeded. 


RESPIRA  TIOF.  409 

It  will  l>e  observed  that  during  quiet  respiration  intrapulmonary  pressure 

(pressure  vnthin  the  lungs)  oscillates  between  negative  and  positive  and  rice 
versd,  whereas  intrathoracic  pressure  (pressure  outside  the  lungs)  is  persistently 
negative,  the  amount  by  which  it  differs  from  atmospheric  pressure  becoming 
greater  during  inspiration  and  diminishing  to  the  previous  level  during  expi- 
ration (p.  397).  Under  forced  expiration,  however,  when  the  air-passages  are 
obstructed  intrathoracic  pressure  may  become  positive.  This  may  be  demon- 
strated in  this  way:  If  a  manometer  be  connected  with  the  mediastinum  of 
a  cadaver,  and  the  chest  be  pulled  upward  in  imitation  of  deep  inspiration, 
intrathoracic  pressure  will  be  found  to  be  about  — 30  millimeters.  If  now  a 
second  manometer  be  connected  with  the  trachea,  and  air  be  forced  into  the 
lungs  through  a  tracheal  tube,  as  intrapulmonary  pressure  rises  intrathoracic 
pressure  falls,  so  that  when  the  former  reaches  +30  millimeters  the  intratho- 
racic negative  pressure  exerted  by  the  elastic  traction  of  the  lungs  is  counter- 
balanced and  the  pressure  within  and  outside  the  lungs  is  equal.  If  intra- 
pulmonary pressure  now  rise  above  this  limit,  intrathoracic  pressure  must 
proportionately  become  positive.  During  violent  coughing,  when  the  expira- 
tory blast  is  obstructed  and  the  muscular  effort  is  powerful,  intrapulmonary 
pressure  may  rise  to  -(-80  millimeters  or  more. 

The  intercostal  tissues  tend  to  be  drawn  inward  as  long  as  negative  intra- 
thoracic pressure  exists,  and  to  be  forced  outward  when  there  is  positive  intra- 
thoracic pressure;  hence  during  inspiration  the  traction  becomes  more  marked 
with  the  rise  of  intrathoracic  pressure,  and  during  expiration  the  reverse ; 
while  during  forced  expiration  with  obstructed  air-passages  the  pressure  exerted 
by  the  effort  of  the  expiratory  muscles,  together  with  the  weight  of  the  chest 
and  the  elastic  reaction  of  the  costal  cartilages,  etc.,  may  be,  as  above  stated, 
far  more  than  sufficient  to  counterbalance  the  traction  exerted  by  the  distended 
elastic  lungs,  and  thus  cause  positive  intrathoracic  pressure. 

The  influences  exerted  by  changes  in  intrathoracic  and  intrapulmonary 
pressure  upon  the  circulation  are  marked  and  important,  and  may  be  so  pro- 
nounced as  to  cause  an  obliteration  of  the  pulse. 

Respiratory  Sounds.— During  the  respiratory  acts  characteristic  sounds 
are  heard  in  the  lungs.  A  study  of  these  sounds,  however,  properly  belongs 
to  physical  diagnosis. 

The  Value  of  Nasal  Breathing. — Nasal  breathing  h;is  a  value  above 
breathing  through  the  mouth,  inasmuch  as  the  air  is  warmed  and  moistened 
and  thus  rendered  more  acceptable  t<>  the  lungs,  mure  or  less  of  the  foreign 
particles   in    the   air  are    removed,  and    noxious   odors    may  be   detected. 

B.  The  Gases  in  the  Lungs,  Blood,  and  Tissues. 

Alterations  in  the  Gases  in  the  Lungs. — The  object  of  respiratory 
movements  is  t<>  renew  the  air  within  the  lungs,  which  air  is  constantly  being 
vitiated,  and  thus  supply  ()  and  remove  CO,  and  other  ell'ete  substances.  The 
lungs  of  the  average  adult  man  after  quiet  expiration  contain  about  2800  cubic 
centimeters  (170  cubic  inches)  of  air.     During  quiet   respiration   there  is  an 


410 


AX    AMEIUCAX    TEXT- BOOK    OF   PHYSIOLOGY. 


inflow  and  outflow  of  about  500  cubic  centimeters  (30  cubic  inches),  therefore 
from  one-sixth  to  one-tilth  of  the  air  in  the  lungs  is  renewed  by  each  act. 
Since  the  respirations  occur  at  so  frequent  a  rate  as  16  to  20  per  minute,  it 
seems  apparent  that  there  must  be  a  rapid  loss  of  O  and  a  gain  of  C02.  This 
is  proven  by  analyses  of  inspired  and  expired  air.  Inspired  air  is  under 
normal  circumstances  atmospheric  air,  composed  of  oxygen,  nitrogen,  argon,  and 
carbon  dioxide,  with  more  or  less  moisture,  traces  of  ammonia  and  nitric  acid, 
dust  and  micro-organisms,  etc.  The  essential  differences  between  inspired 
and  expired  air  are  shown  by  the  following  table,  the  figures  for  the  gases 
being  in  volumes  per  cent.  Nitrogen  and  argon  are  omitted  because  they 
play  no  important  role  in  respiration,  there  being  neither  absorption  nor 
discharge  of  either  to  any  noteworthy  extent.  They  take  no  part,  as  far  as 
known,  beyond  that  of  a  mere  diluent  of  the  inspired  and  expired  air. 


Inspired  air  .    . 
Expired  air  .    . 


20.x  l 
1 1  ;.<>:; 

4.78 


<  ■(  >, 


(Mil 

138 
4.34 


Water  Vapor. 


Variable. 

Saturated. 


Temperature. 


Average  about  20° 
Average,  about  30.3° 


Volume 
(Actual). 


Diminished 


i  .i 


to 


Expired  air  is  therefore  4.78  volumes  per  cent,  poorer  in  O,  4.34  volumes  per 
cent,  richer  in  0O2 ;  it  is  saturated  with  water  vapor,  and  is  of  higher  tem- 
perature and  of  less  actual  volume.  In  addition, expired  air  contains  various 
effete  bodies,  such  as  organic  matter,  hydrogen,  marsh-gas,  etc. 

The  relative  quantities  of  O  absorbed  and  of  0O2  given  off  are  not  constant, 
and  the  ratio  is  known  as  the  respiratory  quotient.    This  is  obtained  by  dividing 

the  volume  of  CO,  given  offby  that  of  ( )  absorbed/     f~^.=  0.908.     Hence, 

O,  4.  i  8 

for  each  volume  of  <)  that  is  lost  0.908  volume  of  C02  is  gained.     Various 

conditions  affect  the  quotient  (p.  436). 

The  quantity  of  watery  vapor  lost  by  the  lungs  varies  inversely  with  the 
amount  contained  in  the  atmosphere  and  with  the  volume  of  air  respired.  The 
less  the  moisture  in  the  atmospheric  air  and  the  larger  the  volume  of  air 
respired,  the  greater  the  loss.  Valentine,  in  experiments  on  eight  young  men, 
records  a  daily  loss  varying  from  319.'.)  to  773.3  grams,  or  an  average  of  540 
grams.  Vierordl  records  a  loss  of  330  grams,  while  Aschenbrandt  estimates 
a  daily  loss  of  526  grams. 

'flie  temperature  of  the  expired  air  varies  directly  with  the  temperature  and 
volume  of  the  inspired  air  and  with  the  temperature  of  the  body.  Valentine  and 
Bruner  found  that  when  the  temperature  of  inspired  air  was  from  15°  to  20°, 
that  iif  expired  air  was  37.3°  ;  when  that  of  inspired  air  was — 6.3°,  expired 
air  had  a  temperature  of  29.8°  ;  while  when  the  inspired  air  was  at  41.9°,  that 
of  expired  air  was  38.1°.  When  the  air  is  respired  through  the  nose  the 
expired  air  is  warmer  than  when  respiration  occurs  through  the  mouth.  Bloeh 1 
1  ZeUschrifl  fur  Ohrenheilhtnde,  1888,  Bd.  xviii.  S.  215. 


R  ESPIRA  TION.  4 1 1 

records  a  difference  of  1.5°  to  2°.  The  figures  by  other  observers  vary  from 
0.5°  to  1.5°.  The  larger  the  volume  of  air  respired,  other  things  being  equal, 
the  less  the  increase  of  temperature. 

The  volume  of  expired  air  is  from  10  to  12  per  cent,  greater  than  that  of 
inspired  air,  this  increase  being  due  to  expansion  caused  by  the  increase  of  tem- 
perature. When  dried  and  proper  deductions  made  for  temperature  and  baro- 
metric pressure,  the  actual  or  corrected  volume  is  less  by  about  ^  to  -£$. 

Lossen  estimated  that  0.0204  gram  of  ammonia  is  eliminated  per  diem  in 
the  expired  air.  Bergey  also  found  small  quantities  of  ammonia,  yet  Voit's 
investigations  indicate  that  expired  air  usually  does  not  contain  even  a  trace 
of  ammonia. 

Alterations  in  the  Gases  in  the  Blood. — The  blood  in  the  pulmonary 
artery  is  of  the  typical  venous  color — that  is,  deep  bluish-red.  During  its 
passage  through  the  lungs  it  becomes  scarlet-red,  or,  commonly  speaking,  arte- 
rialized  or  aerated.  If  we  take  arterial  blood  and  deprive  it  of  oxygen,  the 
color  changes  to  a  venous  hue ;  if  now  we  shake  the  bluish-red  blood  in  air  or 
O,  the  scarlet-red  color  is  restored.  We  have  here  the  suggestion  that  the  blood 
while  passing  through  the  lungs  absorbs  O.  Analyses  show  that  not  only 
does  absorption  of  O  occur,  but  that  there  is  simultaneously  with  this  an 
elimination  from  the  blood  of  C02. 

A  rterial  and  venous  blood  each  contains  approximately  60  volumes  per  cent, 
of  O  and  C02 ;  that  is,  for  about  every  100  volumes  of  blood  60  volumes  of 
gas  will  be  obtained.  Such  analyses  demonstrate  also  that  while  the  total 
volumes  per  cent,  of  O  and  CO,  are  about  the  same,  the  proportions  are 
different.  The  following  table,  compiled  from  various  sources,  gives  the 
volumes  per  cent,  of  gases  in  the  arterial  blood  of  various  animal-  : 

Animal.  Total.                    O.  CO-,.  N. 

Dog 59.38-  18.65  38.93  1.8 

Cat 43.2  13.1  28.8  1.3 

Sheep 57.6  10.7  45.1  1.8 

Rabbit 49.3  13.2  34.0  2.1 

Man 63.4  21.6  40.3  1.5 

Fowl 58.8  10.7  48.1 

Pflviger  obtained  as  averages  of  analyses  of  arterial  blood  of  dogs  58.3 
volumes  per  cent.,  consisting  of  22.2  volumes  per  cent,  of  O,  34.3  volumes 
per  cent,  of  C02,  and  1.8  volumes  per  cent,  of  N.  Venous  blood,  according 
to  estimates  by  Zuntz  based  on  a  large  number  of  analyses,  contains  7.15  vol- 
umes per  cent,  less  of  O  and  8.2  volumes  per  cent,  more  of  C<  I,.  The  quantity 
of  N  is  practically  the  same  in  both  arterial  and  venous  blood. 

The  proportions  of  O  and  COa  in  arterial  blood  vary  but  little  in  speci- 
mens taken  at  random  from  the  arterial  system,  while  those  of  venous  blood, 
on  the  contrary,  differ  considerably  according  to  the  locality  of  the  vessel  as 
well  as  to  the  degree  of  activity  of  the  structures  whence  the  Mood  come-. 
Thus,  venous  blood  from  an  active  secreting  gland  differs  very  little  in  its 
composition,  gaseous  and  otherwise,  from  typical   arterial  blood,  whereas  when 


412  AN    AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

the  gland  is  inactive  the  blood  is  typically  venous.    The  arterial  character  of  the 

venous  blood  in  the  former  ease  is  due  to  the  considerable  increase  in  the  quantity 
of  blood  passing  through  the  gland  during  activity,  the  result  being  that  the  loss 
and  gain  of  substances  are  not  so  noticeable  although  the  total  quantities  of  O 
and  0O2  and  other  substances  exchanged  are  actually  greater  than  when  the 
gland  is  at  rest  and  the  blood  coming  from  it  has  the  typical  venous  characters. 

The  venous  blood  during  its  passage  through  the  lungs  acquires  O  and  loses 
C02.  After  the  blood  is  arterialized  it  parses  from  the  lungs  into  the  left  side 
of  the  heart,  from  which  it  is  forced  to  the  aorta  and  its  ramifications  and  ulti- 
mately into  the  capillaries.  Here  it  undergoes  a  retrograde  change,  parting 
with  some  of  its  O  and  taking  in  exchange  C02;  consequently  the  gaseous 
interchange  between  the  blood  and  the  tissues  is  the  reverse  of  that  occurring 
between  the  blood  and  the  air.  Thus  we  find  that  the  interchange  of  O  and  C02 
occurs  in  a  distinct  series  of  events:  (1)  Oxygen  is  carried  as  a  constituent  of 
the  atmospheric  air  to  the  alveoli ;  (2)  here  it  is  absorbed  by  the  venous  blood, 
which  at  the  same  time  gives  off  C02  to  the  air  in  the  alveoli;  (3)  O  is  now  in 
major  part  conveyed  to  the  tissues,  in  which  it  is  taken  up  and  utilized  in  pro- 
cesses of  oxidation,  CO,  being  the  chief  effete  product,  which  is  formed  immedi- 
ately or  ultimately  and  given  to  the  blood  (a  part  of  the  O  is  consumed  by  the 
blood,  C02  being  one  of  the  results) ;  (4)  the  venous  blood  is  now  conveyed 
to  the  lungs,  C02  is  given  off  and  O  is  received  iu  exchange,  and  the  series  of 
events  is  repeated. 

The  Forces  Concerned  in  the  Diffusion  of  O  and  C02  in  the  Lungs. — 
If  the  air  expired  be  collected  in  a  number  of  parts,  each  successive  portion  will 
be  found  to  contain  a  smaller  percentage  of  O  and  a  larger  percentage  of  C02. 
The  air  in  the  beginning  of  the  respiratory  tract  (nose  and  mouth)  varies  from 
atmospheric  air  but  little  in  composition,  while  that  in  the  alveoli  contains  con- 
siderably less  O  ami  much  more  C02.  With  each  quiet  act  of  inspiration  the 
quantity  of  air  breathed  is  from  three  to  four  times  greater  than  the  capacity  of 
the  trachea  and  bronchi,  so  that  with  each  respiratory  act  two-thirds  or  more 
of  the  fresh  air  is  carried  into  the  alveoli.  When  expiration  occurs  a  similar 
volume  of  the  vitiated  air  within  the  alveoli  is  driven  into  the  bronchi  and 
trachea,  and  thus  a  certain  percentage  is  expelled  from  the  body.  Thus  the 
mere  volume  and  force  of  the  air-currents  must  obviously  be  of  great  value  in 
equalizing  the  composition  of  the  air  in  the  different  parts  of  the  respiratory 
tract. 

The  contractions  of  the  heart  exert  similar  mechanical  influences.  With  each 
contraction  intrathoracic  pressure  is  lessened,  so  that  there  is  a  slight  expansion 
of  the  lungs,  just  as  would  lie  caused  had  the  thorax  been  slightly  enlarged, 
and  consequently  there  is  a  movement  of  air  toward  and  into  the  alveoli.  Dur- 
ing diastole  intrathoracic  pressure  returns  to  the  previous  level,  the  volume 
i if  the  lungs  is  diminished,  and  the  air  is  driven  from  the  alveoli.  Thus 
each  heart-beat  causes  a  to-and-fro  movement  of  the  air.  These  oscilla- 
tions, which  are  termed  cardio-pneumatic  movements,  are  of  more  importance 
than  mighf  seem  at  first  sight,  for  it  has  been  shown  that  in  cases  of  suspended 


BESPIMA  TION.  \\:\ 

animation  and  in  hybernating  animals  they  aid  materially  in  pulmonary  ven- 
tilation. 

Besides  these  mechanical  factors  there  is  present  the  important  factor  of  the 
diffusion  of  gases,  O  diffusing  toward  the  alveoli  and  CG2  toward  the  anterior 
nares.  The  rapidity  with  which  diffusion  occurs,  other  things  being  equal, 
depends  upon  the  differences  in  the  "  partial  pressure  "  of  the  gas  at  various 
regions.  Each  gas  forming  part  of  a  mechanical  mixture  exerts  a  partial 
pressure  proportional  to  its  percentage  of  the  mixture.  Thus,  atmospheric  air 
contains  20.81  volumes  per  cent,  of  O,  0.04  volumes  per  cent,  of  C02,  and  79.15 
volumes  per  cent,  of  N.  If  the  air  exists  at  760  millimeters  barometric  pressure, 
each  gas  will  exert  apart  of  the  total  pressure,  or  a  "  partial  pressure,"  equivalent 
to  its  respective  volume.     Should  we  wish  to  find  the  partial  pressure  of  O,  it 

may  be  ascertained  simply  by  taking  ^jjL  of  the  total  pressure  =  IM^pO 

=  158.15    millimeters;    similarly,  the   partial   pressure    of    C02   would   be 

0.04    X    760        noA      ....  .    .         „AT  79.15X760       nn,  c  t 

r-^j =  0.30  millimeter;  and  that  of  JN,        r-r^r — —  =  601.54 

millimeters.  Knowing,  then,  the  composition  of  any  mixture  of  gases  and  the 
total  pressure  under  which  it  exists,  it  is  a  matter  of  very  simple  calculation 
to  determine  the  partial  pressure  of  each  of  the  various  gases  constituting  the 
atmosphere.  Expired  air  is  poorer  in  O  and  richer  in  C02  than  inspired  air, 
and  alveolar  air  is  altered  even  to  a  greater  extent  than  expired  air ;  hence 
the  partial  pressures  must  be  affected  similarly. 

The  first  portion  of  the  air  expired  contains  a  maximum  amount  of  inspired 
air  and  a  minimum  amount  of  the  air  contained  in  the  air-passages  previous  to 
the  inspiratory  act ;  but  as  expiration  continues  the  mixture  becomes  poorer  and 
poorer  in  inspired  air  and  similarly  richer  in  the  vitiated  air  from  the  smaller 
air-passages  and  the  alveoli;  in  fact,  the  last  portion  of  expired  air  is  very 
similar  to,  if  not  identical  in  its  composition  with,  that  in  the  alveoli.  The 
following  partial  pressures  of  O  and  C02  in  inspired  air  and  alveolar  air 
indicate  the  extent  to  which  the  composition  varies  in  different  parts  of  the 
respiratory  tract : 

Gas.  Inspired  Air.  Alveolar  Air. 

O 158.15  millimeters.  100  millimeters.1 

C02 0.30  millimeter.  23  millimeters. 

Since  the  partial  pressure  of  O  in  inspired  air  is  about  158.15  millimeters,  and 
as  it  is  but  about  100  millimeters  in  the  alveoli,  and  as  the  air  is  poorer  in  ( >  as 
we  pass  from  the  nares  to  the  alveoli,  it  is  obvious  thai  a  force  musi  be  exerted 
constantly  to  cause  a  diffusion  of  O  from  the  larger  air-passages  to  the  bron- 
chioles and  from  the  bronchioles  to  the  alveoli — that  the  ()  must  diffuse 
from  the  region  of  highest  pressure  to  tliat  of  lowest  pressure.  During  life 
an  equilibrium  can  never  be  established,  because  of  the  constant  supply  of 
fresh  air  and  the  continual  passage  of  ()  from   the  alveoli  to  the  blood.     The 

1  The  exact  per  cent,  composition  of  alveolar  air  is  not  known  ;   these  Bgures  are  estimates. 


414  AN  AMERICAN    TEXT- BOOK    OF   PHYSIOLOGY. 

same  relations  of  partial  pressure  are  observed  in  connection  with  C02,  except 
thai  the  air  in  the  alveoli  is  incessantly  acquiring  this  gas  from  the  blood,  causing 
the  per  cent,  composition  of  C02  to  be  much  in  excess  of  that  found  in  the 
atmosphere.  The  partial  pressure  of  COa  in  the  alveolar  air  is  about  23.00 
millimeters,  while  in  inspired  air  it  is  only  0.30  millimeter ;  hence  C02  must 
diffuse  from  the  alveoli  outward. 

There  are,  therefore,  three  important  factors  concerned  in  the  admixture 
and  purification  of  the  air  in  the  lungs:  (1)  The  tidal  movements  caused 
by  inspiration  and  expiration,  which  movements  by  the  mere  force  of  air-cur- 
rents cause  a  partial  mixture  of  the  air;  (2)  the  smaller  wave-movements  (car- 
dio-pneumatie)  produced  by  the  heart-beats,  and  similar  in  effect  to,  but  much 
less  effective  than,  the  first  ;  (3)  the  diffusion  of  O  and  COz,  depending  upon  dif- 
ferences in  their  partial  pressures  in  the  various  parts  of  the  respiratory  tract. 
The  first  is  by  far  the  most  important. 

The  Forces  Concerned  in  the  Interchange  of  O  and  CO.,  between 
the  Alveoli  and  the  Blood. — The  gases  in  the  lungs  are  in  the  form  of 
a  mechanical  mixture,  while  in  the  blood  they  are  in  solution  or  in  chemical 
combination  ;  hence  we  now  have  to  deal  with  conditions  quite  different,  involv- 
ing the  consideration  of  the  relations  of  gases  to  liquids — a  relationship  of 
twofold  nature,  inasmuch  as  the  gas  may  be  found  not  only  in  solution,  but 
in  chemical  association. 

When  an  atmosphere  consisting  of  O,  C02,  and  N  is  brought  in  contact 
with  water,  each  gas  is  absorbed  independently  not  only  of  the  others,  but 
of  the  nature  and  quantity  of  all  other  gases  which  may  happen  to  be  in 
solution.  The  quantity  of  each  gas  dissolved  depends  upon  its  relative  solu- 
bility as  well  as  upon  the  temperature  and  the  barometric  pressure.  The 
coefficient  of  absorption  of  any  fluid  is  the  quantity  of  gas  dissolved  at  a  given 
temperature  and  pressure,  and  is  in  inverse  relation  to  temperature  and  in  direct 
relation  to  pressure.  The  following  absorption-coefficients  of  water  for  O,  C02, 
and  N  at  760  millimeters  of  Hg  have  been  obtained  by  Winkler:1 

Temperature.  O.  C02.  N. 

0° 0.04890  1.7967  0.02348 

15° 0.03415  1.0020  0.01682 

40° 0.02306  •    .  0  01183 

Thus,  at  0°  ( !  and  7f>()  millimeters  pressure  each  volume  of  water  absorbs  0.0489 
volume  of  O;  at  15°,  0.03415  volume;  and  at  40°,  0.02306  volume.  The 
absorption-coefficienl  falls,  it  will  be  observed,  with  the  increase  of  temperature. 
Comparing  the  solubilities  of  the  three  gases,  it  will  be  seen  that  at  the  same 
temperature  and  pressure  a  considerably  larger  quantity  of  CO,  is  absorbed 
than  ofO — Dearly  forty  times  more — whereas  the  quantity  of  N  absorbed  is 
less  than   one-half  as  mneli   as  thai   of  O. 

The  quantity  of  a  gas  absorbed  bya  given  liquid  at  a  given  temperature  is 
proportionate  to  its  coefficient  of  solubility  and  to  the  pressure,  and  is  the  same 
1  Zeittschrift  fur  physikalischi  Chemie,  1892,  Rd.  9,  S.  173. 


BESPIRA  TION.  41 5 

whether  the  gas  exist  free  or  as  a  constituent  of  a  complex  atmosphere,  pro- 
vided that  the  pressure  exerted  by  the  gas  in  both  cases  be  the  same.  Thus, 
atmospheric  air  consists  of  20.81  volumes  per  cent,  of  O,  0.04  volume  per 
cent,  of  C02,  and  79.15  volumes  per  cent,  of  N.  Each  gas  exerts  a  partial 
pressure  in  proportion  to  its  percentage  of  the  mixture.  Assuming  that  the 
air  is  at  standard  atmospheric  pressure,  the  partial  pressure  of  O  is  20.81  per 
cent,  of  760  millimeters  of  Hg,  or  158.15  millimeters.  The  quantity  of  O 
absorbed  from  the  air  at  0°  C  and  760  millimeters  pressure  is  therefore  the  same 
as  when  the  atmosphere  consists  of  pure  O  at  a  pressure  of  158.15  millimeters. 

ti      i  m  •     ,  .11     20.81  X  0.0489         _  ..       _ 

Ihe  absorption-coemcieut  must  consequently  be  -      —  —  =  0.01  vol- 

ume. Therefore  100  volumes  of  water  at  0°  C.  and  760  millimeters  pressure 
absorb  from  the  air  1   volume  of  O. 

If  the  partial  pressure  of  O  be  increased  or  decreased,  the  quantity  absorbed 
will  rise  or  fall  accordingly.  From  this  it  is  obvious  that  O  must  exist  under 
a  certain  degree  of  pressure  to  prevent  its  passing  out  of  solution,  which 
is  expressed  by  the  term  tension  of  solution,  meaning,  in  a  word,  the  pres- 
sure required  to  keep  the  gas  in  solution.  If  the  partial  pressure  of  the  gas 
diminishes,  the  gas  in  solution  is  given  off  until  the  partial  pressure  of  the 
gas  in  the  air  and  the  tension  of  the  gas  in  solution  are  equal.  Conversely,  as 
the  partial  pressure  of  the  gas  in  the  air  increases,  the  gas  in  solution  will  be 
under  correspondingly  higher  tension. 

Tension  of  O. — The  absorption-coefficient  of  blood  for  O  is  nearly  the  same 
as  that  of  water,  so  that  blood  at  0°  should  absorb  from  the  atmosphere  about 
1  volume  per  cent,  of  O,  but  less  than  one-half  as  much  at  the  temperature 
of  the  body.  The  results  of  experiments  show,  however,  that  blood  contains 
considerably  more  than  this  (see  table,  p.  411),  and  very  much  more  than  can 
be  accounted  for  by  the  laws  of  partial  pressures  and  tensions.  Moreover, 
when  the  blood  is  subjected  to  a  vacuum  pump  there  is  evolved  a  small 
amount  of  gas  consistent  with  the  diminution  of  pressure,  but  the  greal  bulk 
of  it  does  not  come  off  until  the  pressure  has  been  reduced  to  -fa  to  -,-1,,  of  an 
atmosphere.  Finally,  the  quantity  absorbed  is  affected  but  little  by  changes 
in  pressure  above  or  below  a  certain  standard.  These  facts  indicate  that 
almost  all  of  the  O  must  be  in  chemical  combination.  This  combination  Is 
with  haemoglobin  in  the  form  of  oxyhemoglobin.  This  chemical  union  i> 
readily  dissociated  at  a  constant  minimal  pressure  which  is  termed  the  tension 
of  dissociation.  There  is  a  persistenl  tendency  of  the  gas  in  such  a  compound 
to  become  disengaged,  so  that  when  oxyhemoglobin  is  placed  under  circum- 
stances where  the  tension  or  the  partial  pressure  of  <>  is  less  than  that  in 
the  compound  dissociation  occurs ;  conversely,  when  haemoglobin  is  brought 
in  contact  with  Oat  a  pressure  above  the  minimal  constanl  of  dissociation 
(..'..  to  ]\t  of  an  atmosphere),  the  two  unite  to  form  oxyhemoglobin.  One 
gram  of  haemoglobin  from  ox  blood  combines,  according  to  Kufner,'  with 
1.34  cubic  centimeters  of  O  at  0°  and  760  millimeters  pressure.  Assuming 
1  Arehiv  fiir  Anatomie  und  Physiologie,  1894,  S.  L30, 


416  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

that  100  cubic  centimeters  of  blood  contain  1 5  grams  of  haemoglobin  (p. 
37),  the  quantity  of  gas  which  would  combine  with  this  amount  of  haemo- 
globin would  be  equal  to  20.1  cubic  centimeters  ;  in  other  words,  arterial 
blood  should  contain,  if  the  haemoglobin  be  saturated  with  oxygen,  20.1 
volumes  per  cent,  of  ( >. 

The  plasma  ami  the  serum  absorb  hut  very  small  quantities  of  O — accord- 
ing to  PHiiger,  only  0.26  volume  per  cent.  ( hving  to  the  relatively  low  absorp- 
tion-coefficient of  the  plasma  compared  with  the  (  ^capacity  of  the  haemoglobin, 
as  well  as  to  the  fact  that  the  haemoglobin  is  nearly  saturated  at  a  relatively 
low  pressure,  the  quantity  of  O  absorbed  is  not  materially  affected  by  an 
increase  of  pressure  above  the  level  of  the  tension  of  dissociation. 

The  tension  of  O  in  arterial  and  venous  blood  must  be  ascertained  separ- 
ately, inasmuch  as  each  contains  a  different  percentage.  Following  this 
method,  Strassburg1  records  the  following  averages:  Arterial  blood,  29.64 
millimeters  of  Hg,  or  3.9  per  cent,  of  an  atmosphere  ;  and  venous  blood, 
22.04  millimeters,  or  2.9  per  cent,  of  an  atmosphere.  The  figures  obtained 
by  Bohr  and  by  Ilaldane  and  Smith2  are,  however,  much  higher  (see  p.  418). 

Tension  of  ( '02. — Venous  blood  contains  about  45  volumes  per  cent,  of 
CO.,.  The  results  of  experiments  prove  that  only  about  5  per  cent,  of  this 
( '( ).,  is  in  simple  solution,  that  from  10  to  20  per  cent,  is  in  firm  chemical 
combination,  and  that  from  75  to  85  per  cent,  is  in  loose  combination. 

When  the  blood  at  the  temperature  of  the  body  is  subjected  to  a  vacuum, 
all  of  the  C02  is  given  off;  but  if  the  blood-corpuscles  be  removed  and  the 
plasma  and  corpuscles  each  in  turn  be  submitted  to  the  pump,  both  will  give 
off  CO,,  the  plasma  yielding  a  larger  volume  than  the  corpuscles,  but  not  so 
much  as  when  they  are  together.  Plasma  and  serum  in  vacuo  give  off  only  a 
portion  of  their  C02;  the  remainder  may,  however,  be  dissociated  by  adding 
acid  or  red  corpuscles.  The  red  corpuscles  therefore  act  as  an  acid  and  cause  the 
disengagement  of  all  the  gas  from  the  plasma;  consequently,  not  only  do  the 
corpuscles  yield  up  the  C02  contained  in  them,  but  they  are  also  active  agents 
in  bringing  about  the  dissociation  of  COz  which  is  in  chemical  combination  in 
the  plasma.  The  dissociation  is  due  in  part,  perhaps,  to  the  presence  of  phos- 
phates in  the  stromata  of  the  red  corpuscles,  and  to  certain  proteids,  but  the 
observations  of  Preyer  and  Hoppe-Seyler  lead  to  the  conviction  that  it  is  due 
chiefly  to  oxyhemoglobin  and  haemoglobin.  While  phosphates,  proteids, 
haemoglobin,  and  oxyhemoglobin  all  may  have  the  power  of  expelling  C02 
from  sodium  carbonate  in  solution  in  vacuo, this  fact  leaves  us  none  the  wiser 
as  to  which,  if  any,  is  active  in  this  way  in  the  blood.  Arterial  blood  gives 
oil' its  CO.,  more  readily  than  venous  blood. 

Of  the  total  quantity  of  0O2,  about  5  per  cent,  is  in  simple  solution  and 
from  10  to  20  per  cent,  is  in  firm  chemical  combination  in  the  plasma,  the  latter 
requiring  the  addition  of  acid  or  of  haemoglobin,  etc.  to  cause  its  dissociation 
in  vacuo;  while  the  remainder,  constituting  much  the  larger  proportion,  is  in 

1  Archivfiir  Physiologic,  Bd.  vi.  S.  65. 

2  Journal  of  Physiology,  1<S!*7,  vol.  xxii.  p.  231. 


RESPIRA  TION.  4 1 7 

loose  chemical  union  in  both  the  plasms  and  the  corpuscles.  That  which  is  in 
chemical  combination  in  the  plasma  is  probably  in  part  combined  with  glob- 
ulin and  alkali,  and  in  part  with  sodium  as  carbonate  and  bicarbonate,  the 
proportion  of  each  varying  with  the  tension  of  the  C02.  The  white  blood- 
corpuscles,  so  far  as  they  contain  any  of  the  C02,  hold  it  probably  in  com- 
bination with  globulin  and  an  alkali,  and  as  carbonates  of  sodium.  The  great 
bulk  of  the  gas  disengaged  from  the  corpuscles  is  derived  from  the  red  cells, 
but  in  what  combination  or  combinations  it  exists  is  not  positively  known. 
The  experiments  of  Setschenow,  Zuntz,  Bohr,1  and  others  indicate  that  it  is 
associated  in  some  obscure  way  with  haemoglobin  which  seems  to  have  the 
powTer  of  combining  with  C02.  This  latter  fact  has  been  shown  by  the  experi- 
ments of  Bohr,  who  compared  the  quantities  of  C02  absorbed  by  pure  water  and 
by  solutions  of  pure  crystallized  haemoglobin  at  constant  temperature  and  varied 
pressure.  He  found  that  the  weight  of  CO,  absorbed  by  the  water  increased  reg- 
ularlv  with  the  increase  of  pressure,  whereas  the  quantity  absorbed  by  the  solu- 
tion of  haemoglobin  was  very  large  relatively  to  the  lower  pressures  and  small 
for  higher  pressures,  and  that  the  increments  of  absorption  were  in  decreasing 
ratio  to  the  rise  of  pressure.  The  absorption  curve  is  therefore  steep  at  first, 
becoming  less  and  less  so  with  the  increase  of  pressure,  and  entirely  different 
from  the  absorption  line  for  pure  water,  which  is  straight.  Moreover,  the 
quantity  of  C02  dissolved  was  considerably  in  excess  of  that  which  physical 
laws  could  permit.  It  is  not  improbable  that  the  O  combines  with  the  pig- 
ment portion  of  the  haemoglobin,  and  the  C02  with  the  proteid  portion.  The 
CO.,,  in  whatever  form  or  forms  it  may  exist  in  the  red  corpuscles,  is  in  looser 
combination  than  in  serum. 

Strassburg's  experiments  show  that  the  average  tension  of  C02  in  arterial 
blood  is  21.28  millimeters  of  Hg,  or  2.8  per  cent,  of  an  atmosphere,  and  in 
venous  blood  41.04  millimeters,  or  5.4  per  cent,  of  an  atmosphere. 

Tension  of  N. — The  quantity  of  nitrogen  in  the  blood  is  about  1.8  volumes 
per  cent.  It  is  in  simple  solution  in  the  blood-plasma,  and  the  quantity  in 
both  venous  and  arterial  blood  is  practically  the  same,  its  presence  and  quan- 
tity are  not  of  physiological  importance.  Argon  has  been  found  in  the  blood 
of  the  horse  by  Regnard  and  Th.  Schlosing  Sohn.2 

The  Interchange  of  O  and  C02  between  the  Alveoli  and  the  Blood. — 
Let  us  now  inquire  into  the  factors  which  bring  about  the  passage  of  O  from 
the  alveoli  to  the  blood  and  of  CG2  from  the  blood  to  the  alveoli.  If  we  have 
two  mixtures  of  the  same  gases,  but  in  unlike  proportions,  and  separate  them 
by  means  of  an  animal  membrane,  diffusion  will  occur  through  the  membrane 
until  the  partial  pressures  of  the  two  gases  are  the  same  on  the  two  sides  of  the 
membrane.  Now  modify  this  experiment  by  bringing  an  atmosphere  of  air 
in  contact  with  water  containing  O,  C02,  and  N  in  solution  or  in  chemical 
combination:  if  the  partial  pressure  of  O  in  the  air  be  greater  than  the  tension 

1  /-.'xprr.  I'ltirrsnch.  u.  d.  Sauerstoffnaufnahme  d.  Blutfarbstoffes,  Copenhagen,  1885  ;  Beilrage  zur 
Physiology,  Festechr.  f.  ('.  Ludwig,  1887,  pp.  1H4-174. 

2  Comptes  rendus  de  I'  Acad,  des  Sci.,  1897,  t.  124,  p.  302. 

Vol.  I.— 27 


418  AN   AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

of  0  in  the  water,  0  will  pass  to  the  water  ;  if  the  partial  pressure  of  CO,  in 
the  air  be  less  than  the  tension  of  COa  in  the  water,  CO,  will  pass  to  the  air. 
It'  now  we  interpose  an  animal  membrane  between  the  atmosphere  and  the 
water,  the  interchange  of  gases  will  continue  as  before.  In  this  ease  we  have 
conditions  analogous  to  those  which  exisl  in  the  living  organism :  In  the  alveoli 
there  i~  an  atmosphere  consisting  of  ().<'<)_,.  and  X  ;  each  gas  is  under  a  par- 
tial pressure  proportional  to  its  volume  per  cent,  of  the  mixture;  the  pul- 
monary membrane  and  the  walls  of  the  capillaries  may  he  regarded  as  a  simple 
animal  membrane  separating  the  air  in  the  alveoli  from  the  blood  ;  finally,  the 
blood  contains  O,  C02,  and  X,  each  of  which  exists  under  a  definite  and 
independent  degree  of  tension.  Whether  or  not  any  or  all  of  these  gases  will 
pass  in  one  direction  or  the  other  must  obviously  depend  upon  the  conditions 
of  partial  pressure  ami  tension  of  each  gas  on  the  two  sides  of  the  membrane. 
The  tension  of  O  in  venous  Mood,  as  above  stated,  is  22.04  millimeters  of 
Hg,  and  of  CO,,  41.04  millimeters.  What  are  the  partial  pressures  of  these 
oases  in  the  alveoli'.'  The  precise  pressures  are  not  known,  but  it  is  esti- 
mated that  the  partial  pressure  of  O  is  about  100  millimeters,  and  of  C02 
aboul   2.'!  millimeters. 

Comparing  the  partial  pressures  and  the  tensions,  as  generally  accepted, 
of  these  two  gases  in  the  alveoli  and  the  blood  respectively,  it  is  obvious  that 
the  conditions  on  the  two  side- of  the  membrane  are  favorable  to  the  diffusion 
of  O  and  CO,,  and  in  definite  but  opposite  direetions.  This  is  illustrated  in 
the  following  diagrammatic  presentation  : 

o.  co2. 

Partial  pressures  in  alveolar  air 100.00  23.00 

Pulmonary  membrane 1 4— — 

Tensions  in  venous  blood 22.04  41.04 

Sine*'  gases  diffuse  from  the  point  of  higher  pressure  or  tension  to  that  of 
lower  pressure  or  tension,  ()  passes  from  the  alveoli  to  the  blood,  while  C02 
passes  from  the  blood  to  the  alveoli. 

It  i-,  however,  impossible  under  certain  conditions,  and  possibly  under 
ordinary  conditions,  to  account  for  the  transmission  of  all  of  either  the  O  or 
the  CO,  by  the  laws  of  diffusion.  Bohr '  found  in  experiments  upon  dogs 
that  the  ten-ion  of  oxygen  in  arterial  blood  is  almost  invariably  higher  than 
the  partial  pressure  of  oxygen  in  the  lungs,  and  in  some  instances  consider- 
ably higher.  His  records  a-  regards  C02,  while  lacking  uniformity,  are  of 
like  import,  and  indicate  that  the  tension  of  CO,  in  the  blood  is  lower  than 
the  partial  pressure  of  this  gas  in  the  lungs.  Although  Bohr's  results  have 
met  with  much  adverse  criticism,  they  have  received  substantial  support  in 
the  recent  researches  of  Haldane  and  Smith"'  on  mice,  birds,  dogs,  and  other 
animals.  They  found  that  the  normal  oxygen  tension  in  arterial  blood  is 
always  higher  than  in  alveolar  air,  and  they  were  consequently  led  to  conclude 

1  Skcmdinavischea  Archivfiir  Physiologie,  1891,  Bd.  ii.  S.  236. 
./  nirnal  <>/  Physiology,  1*07,  vol.  xxii.  p.  231. 


BESPIRA  TION.  4 1 9 

that  the  transmission  of  O  between  the  alveoli  and  the  blood  cannot  be  satis- 
factorily explained  by  mere  diffusion.  Moreover,  about  twice  as  much  argon 
exists  in  solution  in  the  blood  plasma  as  can  be  accounted  for  by  physical 
laws. 

Facts  of  this  kind  are  explicable  on  the  hypothesis  that  the  living  tissues 
are,  as  contended  by  Ludwig,  Bohr,  and  others,  actively  engaged  in  the  proc- 
ess, but  our  knowledge  is  as  yet  too  incomplete  and  contradictory  to  justify 
its  acceptance.  Until,  therefore,  we  are  in  possession  of  the  results  of  further 
research  we  are  justified  in  the  belief  that  the  interchange  of  0  and  ( !< ). 
between  alveoli  and  blood  is  due  to  physical  and  chemical  factors,  diffusion 
being  most  important,  and  that  it  may  be  possible  that  the  living  tissues  take 
some  active  part. 

The  Forces  Concerned  in  the  Interchange  of  O  and  C02  between  the 
Blood  and  the  Tissues. — Innumerable  facts  show  that  the  chief  seat  of  the 
chemical  processes  in  the  body  is  in  the  tissues,  and  that  the  decompositions 
are  essentially  of  an  oxidizing  character  whereby  C02  is  formed  as  one  of 
the  most  important  effete  products ;  consequently  the  blood  as  it  is  carried 
through  the  capillaries  gives  up  O  and  receives  C02. 

Experiments  show  that  the  tissues  exert  a  strong  reducing  action,  and  that 
their  avidity  for  O  is  so  great  that  they  will  take  it  up  at  extremely  low 
pressures.  Moreover,  never  more  than  mere  traces  of  O  can  be  obtained 
from  the  tissues,  because  the  gas  upon  its  absorption  immediately  enters  into 
chemical  combination. 

The  tension  of  0O2  in  the  tissues  is  considerably  higher  than  in  blood. 
Strassburg,1  in  a  loop  of  intestine  into  which  he  injected  atmospheric  air,  found 
that  the  tension  was  58.52  millimeters  of  Hg,  which  is  considerably  greater 
than  in  either  arterial  or  venous  blood.  Thus  we  find  that  the  tension  of  O  in 
the  tissues  is  nil,  owing  to  the  avidity  with  which  substances  of  the  tissues 
combine  with  the  gas,  and  its  chemical  fixation;  while  that  of  (  ( ),  is  very 
high.  Comparing  the  tensions  of  these  two  gases  in  the  blood  and  the 
tissues,  it  will  be  observed  that  there  are  present  conditions  which  arc  highly 
favorable  to  the  passage  of  ()  to  the  tissues  and  of  COa  in  the  reverse  direction  : 


o.  CO,. 

Tensions  in  arterial  blood 29.64  21.28 

Blood-vessel  walls 

Tensions  in  tissues 0.00 


y.b4  S5J.28 

f  i 

0.00  58125 


It  is  manifest  from  the  above  that  O  should  pass  from  the  blood  to  the  tissues, 
and  C02  from  the  tissues  to  the  blood. 

The  lymph  is  probably  merely  a  passive  medium  in  this  interchange.  It 
contains,  according  to  Ham marsten,  only  traces  of  O,  from  37.5  to  17.1  vol- 
umes per  cent,  of  C02,  and  from  1.1  to  1.63  volumes  per  cent,  of  N.  The 
mean  percentage  of  C02  is  lower  than  in  serum,  but  Gaule  has  shown  that  the 
tension  is  higher.      Doubtless  the  same  relations  hold  good  for  the  plasma  and 

1  Lor.  cit. 


420 


AN    AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 


the  bloodj  so  that,  notwithstanding  a  smaller  volume  per  cent,  of  C02  in  the 
lymph,  COa  passes  to  the  1>1< ►< >tl  because  of  the  higher  tension  in  the  lymph. 

Extraction  of  Gases  from  the  Blood. — We  have  found  that  in  the  blood 
both  O  and  C02  exist  partly  in  solution  and  partly  in  chemical  combination. 
The  portion  in  solution  comes  off  regularly  with  a  diminution  of  pressure, 

but  that  which  is  in  chemical  i bination   remains  so  until  the  pressure  is 

reduced  to  the  level  of  the  tension  of  dissociation.  Since  there  are  several 
of  these  combinations,  such  as  O  in  oxyhemoglobin  and  C02  in  carbonates, 
bicarbonates,  etc.,  portions  of  each  of  these  gases  come  oil'  at  different  press- 
ure- in  accordance  with  their  different  tensions  in  the  several  chemical 
combinations.     The  portions  in  solution  may  be  removed  by  the  use  of  an 

ordinary  air-pump,  but  those  in 
chemical  combination  are  held  so 
firmly  that  the  more  powerful  mer- 
curial pump  is  recpiired.  A  con- 
venient pump  of  this  kind  has  been 
devised  by  Dr.  Geo.  T.  Kemp,  the 
description  of  which  he  gives  as 
follows  : 

"  To  use  the  pump  the  reservoir 
bulb  Bb  (Fig.  74),  the  bulb  /,  the 
,  cylinder  SR  and  S'Rf,  and  the  ves- 
sel Pare  filled  with  mercury.  When 
the  bulb  Bb  is  raised  the  mercury 
rises  in  the  tube  AC  and  tills  B, 
driving  the  air  out  by  the  path 
FHOP,  the  stopcock  Q  being  closed. 
When  Bb  is  lowered  again  the  mer- 
cury flows  back  from  B  into  Bb, 
creating  a  Torricellian  vacuum  in 
B.  As  soon  as  the  mercury  has 
fallen  below  the  joint  D,  this 
vacuum  in  B  becomes  connected 
by  the  path  DEG  with  the  tubes 
TGUG'T'  and  the  tube  VWYX,  and 
thence,  when  the  stopcock  is  open, 
with  the  vessel  to  be  exhausted.  The  air  in  this  then  diffuses  to  fill  the 
vacuum  in  II,  and  becomes  rarefied,  so  that  the  mercury  rises  from  the  cylin- 
ders SR  and  S'R'  in  the  outer  tubes  TO  and  T'G'.  The  small  inner  tubes 
RQ  and  R'G'  are  made  so  high  that  even  when  there  is  a  complete  vacuum  in 
the  outer  tubes  TG  and  T'G'  the  mercury  will  not  rise  high  enough  to  cover 
them. 

"On  raising  Bb  again  the  mercury  rises  in  AC,  and  as  soon  as  the  joint  D  is 
covered,  all  the  air  which  has  been  caught  in  B  is  forced  out  by  the  path  FHOP. 
Each  time  the  bulb  Bb  is  raised  and  lowered  a  certain  amount  of  air  is  ex- 


aa  pump. 


RESPIRATION. 


421 


tracted  from  the  receiver,  until  finally  a  vacuum  is  produced.  In  a  similar 
way,  when  the  receiver  connected  with  the  pump  at  Z  contains  any  gas  which 
we  wish  to  analyze — as,  for  example,  the  gases  given  off  by  the  blood  in  a 
vacuum — we  put  a  eudiometer  (Eu)  over  the  bend  of  the  tube  at  P,  which,  of 
course,  is  always  under  the  mercury,  and  collect  the  gases  as  they  are  forced  out. 

"  The  extraction  of  the  last  traces  of  gas  by  raising  and  lowering  Bb  is  a 
very  tedious  and  laborious  process,  so  that  the  final  extraction  of  the  gases  can 
best  be  accomplished  by  the  Sprengel  pump.  IJKLMNHOP.  The  bulb  and  stop- 
cock UK  are  made  separate,  as  shown  in  the  figure,  and  are  connected  with 
LMN  by  a  piece  of  rubber  tubing,  the  whole  being  under  mercury.  This  is 
accomplished  by  the  bend  JKLM,  which  is  made  so  as  to  allow  a  narrow  wooden 
box  filled  with  the  mercury  to  be  slipped  up  over  the  bend  high  enough  to 
cover  the  stopcock  and  thus  prevent  leakage  of  air.  The  same  arrangement  is 
shown  at  X,  and  is  indicated  by  a  dotted  line  in  each  instance.  When  the 
stopcock  K  is  opened  the  mercury  flows  in,  drops  down  the  tube  NHOP,  and 
extracts  the  gases  at  H  in  the  well-known  manner  of  the  Sprengel  pump.  The 
large  bulb  is  for  rapid  exhaustion  down  to  the  last  few  millimeters  of  pressure, 
the  rest  being  accomplished  more  slowly  but  more  perfectly  by  the  Sprengel. 
In  extracting  blood-gases  the  oxygen  is  given  off  suddenly  and  the  C02  slowly. 
The  great  desideratum  is  to  keep  the  tension  of  the  gases  in  the  blood-chamber 
down  as  near  zero  as  possible — certainly  below  20  millimeters  of  Hg.  This 
is  readily  done  with  the  large  bulb  when  the  O  is  evolved,  while  the  Sprengel 
is  able  to  remove  the  C02  as  it  is  given  off,  thus  obviating  the  continued  rais- 
ing and  lowering  of  the  reservoir  bulb." 

The  gases  collected  are  driven  through  the  tube  P  into  a 
eudiometer  previously  filled  with  mercury  and  inverted. 
The  eudiometer  (Fig.  75)  is  a  calibrated  tube  in  which  the 
gases  are  measured.  In  the  upper  part  of  it  are  two  plati- 
num wires  by  means  of  which  an  electric  spark  is  brought 
in  contact  with  the  gases.  Hydrogen  is  introduced  into  the 
eudiometer  in  definite  quantity  (more  than  sufficient  to  com- 
bine with  all  of  the  O  to  form  H2()),  and  a  spark  is  gen- 
erated between  the  ends  of  the  platinum  wires,  causing  the 
Oandthe  II  to  combine.  The  diminution  in  volume  is  now 
noted,  one-third  of  which  diminution  is  equal  to  the  total 
volume  of  O  obtained  from  the  sample  of  blood.  The  quan- 
tity of  COa  may  be  estimated  by  introducing  into  the  eudi- 
ometer a  piece  of  moistened  fused  potassium  hydrate,  which 
absorbs  the  C()2,  forming  potassium  carbonate.  The  loss  in 
volume  is  the  volume  of  C02 obtained  from  the  blood.  The 
residual  gas  consists  of  X  and  II,  the  latter  being  the  excess 
not  combined  with  ().  The  total  quantity  of  II  introduced  Fiq. 75.-Eudiometer. 
being  known,  and  also  the  quantity  which  combined  with 
(),  the  difference  is  deducted  from  the  volume  N  and  II,  the  remainder  being 
the  volume  N.     Accurate  analysis  necessitates  correction-  for  temperature,  for 


>    I!  , 


422 


AN    AMERICAN    TEXT- IK >< >K    OF  PHYSIOLOGY. 


tension  "I'  aqueous  vapor,  and  for  atmospheric  pressure,  as  well  as  attention  to 
the  many  details  connected  with  gas-analysis. 

Cutaneous  Respiration. — In  frogs  the  skin  is  a  more  important  respi- 
ratory  organ  than  the  lungs,  as  is  illustrated  by  the  fact  that  asphyxia  is 
more  rapidly  produced  by  dipping  the  animal  in  oil,  and  thus  preventing  the 
interchange  of  ()  and  COa  through  the  skin,  than  by  ligature  of  the  trachea; 
moreover,the  investigations  of  Regnault  and  Reiset  show  that  in  these  animals 
Dearly  the  same  quantities  of  O  are  absorbed  and  C02  eliminated  after  the 
lungs  are  excised  as  in  the  intaet  animal.  In  man  the  reverse  is  the  case,  the 
cutaneous  interchange  being  insignificant  as  compared  with  that  in  the  lungs. 

The  quantity  of  CO.,  exhaled  through  the  skin  during  twenty-four  hours 
has  been  estimated  by  different  observers  from  2.23  grams  to  as  much  as  32.08 
grams.  Compared  with  pulmonary  interchange,  the  ratio  of  O  absorbed  is 
probably  about  1  :  100-200,  and  of  C02  eliminated,  1  :  200-250. 

(  utaneous  respiration  is,  as  a  rule,  subject  to  the  same  circumstances  that 
affect  the  interchange  in  the  luugs,  and  is  accomplished,  moreover,  in  the  same 
way.  In  some  instances,  however,  it  is  influenced  in  the  opposite  direction ; 
for  instance,  it  is  increased  by  circumstances  that  hinder  pulmonary  respiration. 
Cutaneous  respiration  is  favored  by  moist  skin,  and  Ronchi  found  that  it  was 
increased  by  higher  external  temperature. 

Internal  or  Tissue-respiration. — The  main  object  of  the  respiratory  mech- 
anism is  to  supply  the  organism  with  O  and  to  remove  the  C02  resulting  from 
ti->ue-activitv.  The  organism  may  be  regarded  as  an  aggregation  of  living 
cells,  each  of  which  during  life  consumes  O  and  gives  off  COz.  Activity 
depends  essentially  upon  processes  of  oxidation  ;  consequently,  not  only  is  oxi- 
dation necessary  for  existence,  but  the  quantity  of  O  absorbed  must  bear  a  direct 
relation  to  the  degree  of  activity.  The  avidity  of  the  different  tissues  for  O 
varies  greatly,  and  the  differences  are  doubtless  expressions,  broadly  speaking, 
of  the  relative  intensities  of  their  respiratory  processes.  Quinquaud 1  records 
the  following  absorption-capacities  of  100  grams  of  each  tissue,  submitted  for 
three  hours  to  a  temperature  of  38°  : 


Muscle 23  c.c. 

I  hart 21    " 

Brain 12  " 

Liver 10    " 

Kidney 10    " 


Spleen 8 

Lungs 7.2 

Adipose  tissue 6 

Bone 5 

Blood 0.8 


The  quantity  of  ('()_,  formed  in  each  case  was  approximately  proportional  to 
the  quantity  of  <  )  absorbed.  The  respiratory  value  of  blood  is  doubtless  too 
low.  The  blood  is  not  merely  a  carrier  of  O  aud  C02  to  and  from  the  tissues, 
but  is  itself  th''  -eat  of  active  disintegrations  which  involve  the  consumption 
of  O  and  the  production  of  C02  and  other  effete  matters.  Ludwig  and  his 
pupils  Ion-  ago  showed  that  when  readily-oxidizable  substances,  such  as  lactate 
of  sodium,  are  mixed  with  the  blood,  and  the  blood  is  transfused  through  the 
lung-  or  other  living  tissues,  more  <  >  is  consumed  and  C02  given  off  than  by 
1  Complet  rendua  de  /«  Societe  de  biohgu  (9),  1890,  2,  pp.  29,  30. 


RESPIRATIOX.  423 

blood  free  from  them.  These  results  have  been  substantiated  by  the  recent 
researches  of  Bohr  and  Henriquez1  on  dogs,  whose  experiments  have  further 
shown  that  a  considerable  portion  of  O  may  disappear  as  a  result  of  processes 
occurring  in  the  blood  during  its  passage  through  the  lungs,  and  a  large 
amount  of  C02  be  formed  as  one  of  the  products.  Thus  they  found  that  con- 
siderably more  O  was  absorbed  from  the  lungs  than  could  be  pumped  from  the 
blood,  and  that  more  C02  was  given  to  the  air  in  the  lungs  than  was  lost 
by  the  venous  blood.  They  believe  that  the  tissues  deliver  to  the  blood  par- 
tially-oxidized substances  which  undergo  a  final  splitting  up  when  the  blood 
reaches  the  lungs.  If  this  be  so,  the  respiratory  capacity  of  the  blood,  apart 
from  its  capacity  as  a  carrier  of  0  and  C02  to  and  from  the  tissues,  must  be 
considerably  greater  than  indicated  by  Quinquaud's  figures. 

The  chief  chemical  product  of  the  oxidative  decompositions  in  the  blood 
and  tissues  is  C02 ;  but  the  quantity  of  O  absorbed  is  not  necessarilv  related 
to  the  amount  of  C02  eliminated  ;  that  is,  during  a  given  interval  the  quantity 
of  O  may  be  out  of  proportion  to  the  elimination  of  C02,  and  vice  versd. 
Thus,  in  a  muscle  during  rest,  at  normal  bodily  temperature,  the  consumption 
of  O  is  greater  than  the  elimination  of  C02,  while  during  activity  the  propor- 
tion of  C02  to  O  increases  and  may  exceed  that  of  O.  Rubner's2  experiments 
on  the  resting  muscle  at  various  temperatures  accentuate  the  fact  that  the  for- 
mation of  C02  may  be  independent  of  the  quantity  of  O  absorbed.  Thus,  at 
8.4°  the  respiratory  quotient  was  3.28  ;  at  28.2°,  1.01  ;  at  33.8°,  1.18 ;  and  at 
38.8°,  0.91.  The  high  respiratory  quotient  at  low  temperatures  is  to  be 
explained  partly  by  direct  oxidation  and  partly  by  intramolecular  splitting, 
which  is  independent  of  oxidation.  It  is  probable  that  during  rest  O  is  util- 
ized to  some  extent  in  oxidations  which  are  not  at  once  carried  to  their  final 
stage  and  in  which  relatively  little  C02  is  formed;  hence  during  activity  com- 
paratively little  O  is  required  to  cause  a  final  disintegration  of  the  now  par- 
tially broken-down  substances,  and  thus  to  give  rise  to  a  relatively  large 
formation  of  C02.  (See  Effects  of  Muscular  Activity  on  Respiration  and 
Metabolism  of  Muscle,  etc.) 

C.  The  Rhythm,  Frequency,  and  Depth  of  the  Respiratory 

Movements. 

The  Rhythm  of  the  Respiratory  Movements. — During  normal  breathing 
the  respiratory  movements  follow  each  other  in  regular  sequence  or  rhythm. 
Various  instruments  have  been  devised  for  the  study  of  these  movements 
in  man;  the  form  most  commonly  used  is  the  stethograph  or  pneumo- 
graph of  Marey.  The  respiratory  movements  are  communicated  by  a  system 
of  levers  to  a  tambour,  thence  through  a  rubber  tube  to  a  second  tambour 
having  attached  a  lever  which  records  upon  a  moving  surface.  In  animals 
:i  trachea]  cannula  or  tube  (p.  I  16)  Is  usually  Inserted  into  the  trachea,  and 
a  tube  is   led    from    it  to  a  recording  tambour.       In   case  the   movements 

1  Comptes  rendus,  1892,  t.   Ill,  pp.   1496-99. 

2  DtiBois-Rfijmond's  Archiv  fur  Physiologie,  1885,  S.  38-66. 


I-Jl  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

of  the  ribs  are  especially  to  be  studied,  the  stethograph  maybe  employed; 
if  the  movements  of  the  diaphragm,  a  long  probe  may  be  inserted 
through  the  abdominal  walls  so  that  one  end  rests  between  the  liver  and  the 
diaphragm  and  the  other  end  connects  with  a  recording  lever,  the  abdominal 
walls  serving  as  a  fulcrum.  A  tracing  obtained  by  one  of  the  above  methods 
shows:  (1)  That  inspiration  passes  into  expiration  without  an  appreciable  in- 
tervening pause;  (2)  that  inspiration  is  shorter  than  expiration;  (3)  that  the 
curves  of  inspiration  and  expiration  differ  in  certain  characters.  The  relative 
periods  of  inspiration  and  expiration  vary  with  age,  sex,  and  other  conditions. 
The  inspiratory  phase  is  shorter  relatively  in  women  than  in  men.  and  in  chil- 
dren and  the  aged  than  in  those  of  middle  life.  The  length  of  inspiration  as 
compared  to  expiration  is  subject  to  variations,  but  these  relations  are  affected 
chiefly  by  disease  and  by  other  abnormal  conditions.  After  section  of  the 
pneumogastric  nerves,  and  in  diseased  conditions  which  narrow  any  part  of  the 
air-passages,  inspiration  is  longer  than  expiration,  while  in  emphysema  the 
expiratory  phase  is  prolonged.  The  relative  periods  occupied  by  inspiration 
and  by  expiration  in  the  adult  differ  according  to  various  observers;  at  one 
extreme,  the  ratio  according  to  Vierordt  and  Ludwig  is  10  :  19-20,  and  at 
the  other  extreme,  according  to  Ewald,  11:12.  A  mean  ratio  is  5:6. 
Rennebaum  found  that  the  expiratory  phase  is  relatively  prolonged  by  an 
increase  in  the  respiration-rate,  the  ratio  being  9  :  10  at  13  respirations  per 
minute,  and  9  :  13  at  46  per  minute.  In  the  new-born  the  ratio  is  1  :  2-3. 
Mosso  found  that  during  sleep  the  inspiratory  phase  is  lengthened  one-fourth. 

Inspiration  is  more  abrupt  than  expiration,  the  lever  moving  more  rapidly 
during  inspiration  than  during  expiration;  consequently  the  curves  differ  in 
character.  We  may  volitionally  affect  the  rhythm  and  the  various  phases  of 
each  respiratory  act. 

A  pause  may  exist  between  expiration  and  inspiration  (expiratory  pause) 
when  the  respirations  are  abnormally  infrequent.  In  certain  diseases  an  inter- 
val may  be  observed  between  inspiration  and  expiration  (inspiratory  pause). 
Some  observers  look  upon  the  nearly  horizontal  part  of  the  respiratory  curve 
a-  a  record  of  a  pause,  but  an  examination  of  tracings  of  normal  respirations 
shows  that  one  phase  passes  into  the  other  without  an  appreciable  interval. 

The  respiratory  acts  while  we  are  awake  and  quiet  are  rhythmical,  but  this 
rhythm  is  more  or  less  disturbed  during  sleep,  especially  in  young  children 
ami  in  the  aged.  In  the  latter  there  may  not  only  be  an  irregularity  in 
the  time-intervals  between  successive  acts,  but  occasionally  long  expiratory 
pauses,  giving  the  movements  a  peculiar  periodical  character.  In  the  so-called 
"  Cheyne-Stokes  respiration  "  the  rhythm  is .  greatly  disturbed.  This  type  is 
characterized  by  groups  of  respiratory  movements,  each  group  being  separated 
from  the  preceding  and  succeeding  ones  by  more  or  less  marked  pauses.  The 
fir>t  respiration  in  each  group  is  very  shallow  and  is  followed  by  movements 
which  successively  become  deeper  and  deeper  until  a  maximum  is  reached; 
then  the  successive  movements  become  more  and  more  shallow  and  finally 
<•< ase.      Bach  group  commonly  consists  of  about   10  to  30  respirations,  and  is 


BESPIBA  TION.  A  2  5 

separated  from  the  preceding  and  succeeding  groups  by  a  variable  interval, 
usually  30  to  45  seconds.  This  form  of  respiration  is  frequently  observed  in 
uraemia,  after  severe  hemorrhage,  and  in  certain  diseases  of  the  heart  and  brain. 
Periodical  alterations  in  the  respiratory  rhythm  may  be  observed  in  the  last 
stages  of  asphyxia,  in  poisoning  by  chloral,  opium,  curare,  and  digitalis,  in  cer- 
tain septic  fevers,  in  certain  animals  during  hybernation,  ete.  In  the  human 
organism,  excepting  during  sleep  and  in  the  aged  and  the  very  young,  such 
non-rhythmical  respirations  are  always  indicative  of  abnormal  conditions. 

In  warm-blooded  animals  the  movements  are  generally  of  a  much  more 
rhythmical  character  than  in  cold-blooded  animals. 

The  Frequency  and  Depth  of  the  Respiratory  Movements. — The 
respiratory  rate  is  affected  by  a  number  of  conditions,  chiefly  species,  age, 
posture,  time  of  day,  digestion,  activity,  internal  and  external  temperature, 
season,  barometric  pressure,  emotions,  the  composition  of  the  air,  the  composi- 
tion of  the  blood,  the  state  of  the  respiratory  centres  and  nerves,  etc. 

The  following  figures,  compiled  from  various  sources,  indicate  the  wide 
differences  in  various  species,  the  rates  being  per  minute  : 


Horse 6-10 

Ox 10-15 

Sheep 12-20 


Pig 15-20 

Man 16-24 

Cat 20-30 


Dog 15-25  Pigeon 30 


Kabbit  ....  50-60 

Sparrow    ...  90 

Guinea-pig  .    .  100-150 

Rat 100-200 


The  average  rate  in  man  varies  according  to  different  investigators,  from 
11.9  by  Vierordt  to  19.35  by  Ruef.  Hutchinson  noted  16-24  per  minute  as 
a  mean  of  2000  observations.  There  is  a  general,  but  not  an  absolute,  rela- 
tionship between  the  rate  and  the  size  of  the  body,  as  regards  both  different 
species  and  different  individuals  of  the  same  species :  as  a  rule,  the  smaller  the 
species  the  more  frequent  the  respirations ;  the  same  holding  good  for  indi- 
viduals of  the  same  species. 

The  marked  influence  of  age  is  illustrated  by  the  records  of  the  observa- 
tions by  Quetelet  on  300  individuals  : 

Rate  per  Minute. 
Age. 

New-born 70 

1-  5  years     .    .    . 

15-20     "         


20-25 
25-30 
30-50 


cimum. 

Minimum. 

Mean. 

70 

23 

44 

32 

26 

24 

16 

20 

24 

14 

18.7 

21 

15 

16 

23 

11 

18.1 

Posture  exerts  a  marked  influence,  especially  in  those  enfeebled  by  disease. 
Guy  records,  in  normal  individuals,  13  while  lying,  19  while  sitting,  and  22 
while  standing. 

The  diurnal  changes  are  in  close  accord  with  those  of  the  pulse-rale  (p.  1  21  i. 
The  rate  is  less  frequent  by  about  one-fourth  during  the  night  than  during  the 
day,  and  more  frequent  after  meals,  especially  alter  the  mid-day  meal.  Vier- 
ordt noted  the  following  variations:  9  a.m.,  12.1  ;    12  m.,  11.5;  2  P.M.,  13 J 


126  AX  AMERICAS    TEXT-BOOK    OF  PHYSIOLOGY. 

7  P.M.,  11.1.  Guy  gives  the  mean  rate  in  the  morning  as  17  and  in  the 
evening  as  18. 

The  rate  increases  with  an  increase  in  muscular  activity  (p.  121). 

Changes  in  external  (surrounding)  temperature  have  very  little  influence. 
Vierordt  noted  a  rate  of  12.16  at  <s.47°  C.  and  one  of  11.57  at  19.4°  C,  and 
that  an  increase  of  each  degree  C  increases  the  period  of  each  respiration 
about  .,1lltli,  thus  lessening  the  rate.  Alterations  «>f  internal  temperature  are 
associated  with  marked  changes,  as  is  well   illustrated  in  the  increase  in  the 

■ 

rate  observed  in  lexers,  which  increase,  in  turn,  is  closely  related  to  the  rise 
in  the  pulse-rate  and  the  body  temperature. 

Season  is  not  without  its  influence.  In  the  spring  the  rate,  according  to  E. 
Smith,  is  32  per  cent,  greater  than  at  the  end  of  summer. 

Ordinary  changes  in  atmospheric  pressure  exert  no  influence,  but  under  con- 
siderable variations  the  rate  rises  and  falls  inversely  with  the  pressure. 

The  frequency  of  the  respirations  may  be  profoundly  affected  by  our  emo- 
tions and  by  our  will.  Mental  excitement  may  increase  or  decrease  the  rate, 
and,  as  is  well  known,  we  may  greatly  modify  not  only  the  rate,  but  also  the 
depth  and  the  rhythm  of  the  movements  by  volitional  effort. 

If  the  composition  of  the  inspired  air  becomes  so  altered  that  O  falls  below 
13  volumes  per  cent.,  the  respirations  are  increased  in  frequency  and  in  depth. 
In  the  same  way,  if  the  blood  becomes  deficient  in  O  or  overcharged  with  C02, 
movements  of  respiration  are  increased. 

Excitation  and  depression  of  the  respiratory  centres  and  nerves  through  the 
agency  of  operations,  disease,  poisons,  etc.  effect  changes  in  the  respiratory  rate. 

The  rate  and  the  depth  of  the  respirations  bear  generally  an  inverse  relation 
to  each  other  :  the  greater  the  rate  the  less  the  depth,  and  vice  versa  ;  but  the 
quantity  of  air  respired  during  a  given  period  does  not  necessarily  bear  any 
direct  relation  to  either  the  rate  or  the  depth  alone,  but  rather  to  both. 

A  general  relationship  exists  between  the  frequency  of  the  respirations  and 
the  pulse-rate.  Comparisons  of  a  large  number  of  observations  by  different 
investigators  give  a  ratio  at  twenty-five  to  thirty-five  years,  1  :  4-4.5  ;  at 
fifteen  to  twenty  years,  1  :  3.5 ;  at  six  weeks,  1  :  2.5. 


D.  The  Volumes  of  Air,  O,  and  CO..  Respired. 
During  quiet  respiration  there  occurs  an  inflow  and  outflow  of  air,  desig- 
nated tidal  air,  equal  to  about  500  cubic  centimeters,  or  30  cubic  inches.  The 
volume  of  expired  air  is  a  little  in  excess  of  inspired  air,  owing  to  the  expan- 
sion caused  by  the  increase  of  temperature,  although  the  actual  volume  is  less 
(p.  410).  The  volume  of  air  respired  during  each  respiration  bears  generally 
an  inverse  relation  to  the  respiration-rate,  and  is  affected  by  the  position  of  the 
body;  thus,  if  in  the  lying  posture  the  volume  be  1,  when  sitting  it  will  be 
1.11,  and  when  standing  1.13  (Hutchinson).  Besides  the  term  tidal  air, 
others  are  used  to  express  definite  volumes  associated  with  the  capacity 
of   the  lungs  under  certain  circumstances.       Thus,  Hutchinson  distinguishes 


RESPIBATIOX. 


127 


complemented  air,  or  the  volume  that  can  be  inspired  after  the  completion  of  an 
ordinary  inspiration  (1500  cubic  centimeters);  reserve  or  supplemental  air,  or 
the  volume  that  can  be  expelled  after  an  ordinary  expiration  (1240-1800  cubic 
centimeters);  residual  air,  or  the  volume  remaining  in  the  lungs  after  the  most 
forcible  expiration  (1230-1(340  cubic  centimeters);  and  stationary  air,  or  the 
volume  remaining  in  the  lungs  after  ordinary  expiration,  and  equal  to 
reserve  air  plus  residual  air  (2470-3440  cubic  centimeters).  The  volume  of 
residual  air  is  different  according  to  various  observers,  the  estimates  ranging 
within  wide  limits.  Hermann  and  Berenstein1  record  from  observations 
on  sixteen  living  male  subjects  a  maximum  of  1250  cubic  centimeters, 
a  minimum  of  440  cubic  centimeters,  and  a  mean  of  796  cubic  centi- 
meters. 

Lung-capacity  is  the  total  quantity  of  air  the  lungs  contain  after  the  most 
forcible  inspiration,  and  is  equal  to  the  vital  capacity  plus  the  residual  air. 

Bronchial  capacity  is  the  capacity  of  the 
trachea  and  bronchi,  and  is  equal  to  about  140 
cubic  centimeters. 

Alveolar  capacity  is  the  volume  of  air  in 
the  smallest  air-passages  and  alveoli,  and  is 
greater  during  inspiration  than  during  expira- 
tion, and,  of  course,  is  altered  in  proportion  to 
the  depth  of  these  movements.  After  quiet 
expiration  it  is  equal  to  about  2000  to  3000 
cubic  centimeters ;  during  quiet  inspiration  it 
is  increased  about  500  cubic  centimeters,  and 
during  forced  inspiration  about  2000  cubic  cen- 
timeters; during  forced  expiration  it  is  dimin- 
ished about  1500  cubic  centimeters.  Between 
the  extremes  of  forced  inspiration  and  forced 
expiration   the  volume  differs  about  3J  times. 

Vit<il  capacity  is  the  volume  of  air  that  can 
be  expired  after  the  most  forcible  inspiration. 
Averages  obtained  by  Vierordt  from  the  results 
of  the  observations  by  various  investigators  are 
3400  cubic  centimeters  for  men  and  2500  cubic 
centimeters  for  women.  Such  investigations 
are  conducted  by  the  aid  of  a  spirometer  (Fig. 
76),  which  is  a  calibrated  gasometer  consisting 
of  a  bell-jar  submerged  in  water  and  counter- 
poised. Communicating  with  the  interior  of 
the  jar  is  a  tube  through  which  the  expired  air 

is  conducted.     The  subject   makes  the  deepest  possible  inspiration  ami   then 
forcibly  expires   into  the  tube:   the  jar  rises  in   proportion   to  the  volume  of 
air  admitted,  and  the  extent  of  this  rise  may  be  read   from  the  scale. 
1  Archiv  fiir  die  gesammte  Physiologie,  1891,  Bd.  ^K  S.  363. 


76.— Wintrich'a   modification  of 
Butchinson'B  spirometer. 


428  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

Vital  capacity  is  affected  by  various  circumstances,  especially  age,  stature, 
sex,  posture,  occupation,  and  disease.  It  increases  with  age,  reaching  a  maxi- 
mum at  about  thirty-five  years,  after  which  there  occurs  an  annual  decrease  of 
about  32  cubic  centimeters  up  to  about  sixty-five  years.  In  proportion  to 
the  length  of  the  body  it  increases  up  to  twenty-five  years  and  then  dimin- 
ishes. Wintrich  has  shown  that  vital  capacity  for  each  centimeter  of  height 
varies  at  different  ages;  thus  at  eight  to  ten  years  it  is  9  to  11  cubic 
centimeters  for  each  centimeter  of  height,  at  sixteen  to  eighteen  years 
20.65  cubic  centimeters,  and  at  fifty  years  21  cubic  centimeters.  Arnold 
estimates  that  in  the  adult  for  each  centimeter  of  increase  or  decrease  of 
height  beyond  a  mean  standard  there  is  a  corresponding  rise  or  fall  of  60  cubic 
centimeters  in  men  and  of  40  cubic  centimeters  in  women.  It  is  greater  in 
men  than  in  women  of  the  same  height,  the  ratio  being  about  10  :  7.5.  Hutch- 
inson found  that  it  was  affected  by  posture,  the  ratios  being  as  follows :  Lying 
on  chest  and  abdomen,  0.96;  lying  on  back  or  sitting,  1.11;  and  standing, 
1.13.  Wintrich  and  Arnold  both  have  found  that  vital  capacity  is  diminished 
during  starvation  100  to  200  cubic  centimeters.  Physical  exercise,  such  as 
running  and  other  forms  of  violent  exertion  that  increase  the  rate  and  depth 
of  respiration,  tends  to  increase  the  vital  capacity.  Occupation  also  exerts 
an  influence  upon  vital  capacity,  it  being  proportionately  greater  in  those  en- 
gaged in  active  physical  work  than  in  those  leading  a  sedentary  life.  All  cir- 
cumstances which  interfere  with  the  full  and  free  expansion  of  the  thoracic 
cavitv  diminish  vital  capacity,  as,  for  instance,  tight  clothing,  visceral  tumors, 
tuberculosis  of  the  lungs,  pneumothorax,  etc. 

The  Volumes  of  O  and  C02  Respired. — The  quantity  of  air  re- 
spired during  each  respiratory  act  is  about  500  cubic  centimeters,  or  30  cubic 
inches;  and  since  the  normal  respiration-rate  in  man  is,  we  may  say,  for  the 
twenty-four  hours  about  15,  the  total  quantity  of  air  respired  per  diem  may 
readily  be  calculated  : 

Per  minute,  500  c.c.         x  15  =    7,500  c.c,  or  7.5  liters. 
Per  hour,  7.5  liters  x  60  =       450  liters. 

Per  dav,        450      liters  x  24  =  10,800  liters,  or  abonl  380  cubic  feet,  which  is  equal  to  a  volume 

about  220  centimeters  ( 7 J  feet)  in  height,width,  and  thickness. 

With  these  figures  as  standards,  and  knowing  the  per  cent,  composition  of 
inspired  and  expired  air,  the  volumes  of  O  absorbed  and  of  CC)2  eliminated 
are  easily  found.  The  inspired  air  loses  4.78  volumes  per  cent,  of  O;  it  is 
obvious,  then,  that  the  quantity  absorbed  per  diem  is  4.78  volumes  percent, 
of  10,800  liters,  which  is  516  liters,  or  about  740  grams;  likewise,  the  ex- 
pired nir  contains  an  excess  of  4.34  volumes  per  cent,  of  C02;  the  quantity 
expired  per  diem  is  4.34  volumes  per  cent,  of  10,800  liters,  or  470  liters  or 
925  grams.  These  figures,  while  not  strictly  accurate,  are  in  accord  with  those 
obtained  by  other  methods  of  estimation  and  by  experiments.  The  amount  of 
O  varies  from  600  to  1200  grams  per  diem,  and  that  of  C02  from  700  to 
1400  grams — approximate  averages  being  about  750  grams  of  O  and  875 
gram-  n{  COa. 


RESPIRA  TIOJV. 


429 


The  quantities  of  0  and  of  C02  exchanged,  although  in  a  general  way 
closely  related,  are  in  a  measure  independent  of  each  other,  but,  as  a  rule,  an 
increase  or  a  decrease  in  one  is  accompanied  by  a  rise  or  a  fall  in  the  other. 
The  most  important  conditions  affecting  the  quantities  of  O  absorbed  and  ( '( )., 
given  off  are  species,  body-weight  and  body-surface,  age,  sex,  constitution,  rate 
and  depth  of  the  respirations,  the  period  of  the  day,  digestion,  food,  internal 
and  external  temperature,  activity,  atmospheric  pressure,  the  composition  of 
the  inspired  air,  and  the  condition  of  the  nervous  system. 

Most  of  the  studies  have  been  made  solely  by  determinations  of  the  quan- 
tities of  C02  given  off,  the  results  being  taken  as  standards  for  the  relative 
volumes  of  O  absorbed ;  but  such  deductions  are  of  very  uncertain  value  and 
may  be  entirely  misleading.     (See  Respiratory  Quotient,  p.  436.) 

Respiratory  activity  in  different  species  in  proportion  to  body-weight  is  less 
in  cold-blooded  than  in  warm-blooded  animals,  the  difference  being  due  chiefly 
to  the  larger  supply  of  O  demanded  by  the  more  active  heat-producing  pro- 
cesses in  the  latter,  and  in  part  to  the  more  active  character  generally  of  the 
bodily  operations.  If  we  take  as  a  standard  for  cold-blooded  animals  the 
respiratory  activity  in  the  frog  (which  is  0.07  gram  of  O  per  kilogram  of  body- 
weight  per  hour),  and  compare  this  with  the  standards  for  warm-blooded  ani- 
mals, in  the  latter  it  will  be  from  6  to  18  times  greater,  according  to  the  species. 
Respiratory  activity  is  higher  in  proportion  to  body-weight  in  birds  than  in 
mammals.  The  following  tabular  statement  of  the  intensity  of  the  respiratory 
interchange  per  kilogram  of  body-weight  per  hour,  compiled  chiefly  from  the 
researches  of  Regnault  and  Reiset,  Zuntz  and  Lehman n,  Bossignault,  Herzog, 
and  Grouven,  illustrates  these  differences : 


Animal. 


Finch  . 
Sparrow 

Fowl  .  . 

Frog  .  . 

Dog    .  . 

Cat     .  . 

Ox.    .  . 

Ass     .  . 

Calf    .  . 

Horse  . 

Sheep  . 

Babbit  . 
Man 

Pig     .  . 


0. 

co2. 

Grams. 

C.c. 

Grams. 

C.c. 

11.635 

1837 

11.540 

5857 

9.595 

6710 

10.492 

5334 

1.189 

831 

1.271 

678 

0.070 

49 

0.062 

37 

1.191 

847 

1.281 

652 

1.001 

699 

1.082 

549 

0.550 

382 

0.757 

383 

0.566 

394 

0.393 

394 

0.481 

336 

0.571 

290 

0.437 

303 

0.640 

323 

0.499 

347 

0.599 

304 

0.920 

642 

1  1 58 

588 

0.434 

302 

0.507 

.'57 

0.471 

331 

0.594 

302 

CO; 

o 


0.72 

0.79 
0.S2 
0.76 
0.77 
0.80 
1.00 
1.00 

o.st; 
0.9J 
o.ss 
0.90 
0.85 
0.91 


As  a  rule,  the  smaller  the  species  the  greater  (relatively,  but  not  absolutely) 
is  the  intensity  of  respiratory  activity;  for  instance,  the  consumption  of  O 
for  each  kilogram  of  body-weight  is  for  the  horse,  <).  137  ;  ass,  0.566  ;  sheep, 
0.499;  rabbit,  0.92;  and  for  birds,  as  high  as  12.58.  For  differenl  species 
of  the  same  class  the  same  variations  are  observed  ;  thus,  Richel  records,  as 
the  result  of  investigations  on  birds,  the  following  figures  as  the  number  of 


130 


AN  AMERICAN    TEXT-BOOK   OE  PHYSIOLOGY. 


grams  of  C02  given  off  per  kilogram  of  body-weight  per  hour:  Goose,  1.49; 
fowl,  1.66;  duck,  2.27;  pigeon,  3.36;  and  finch,  12.58. 

In  the  same  species,  other  things  being  equal,  the  respiratory  interchange  is 
greater  in  smaller  animals,  because  in  relation  to  body-weight  the  body-surface 
is  greater,  causing  a  greater  proportional  heat-loss,  which  in  turn  necessitates  a 
larger  consumption  of  O  for  oxidative  processes  to  produce  heat,  and  a  conse- 
quent increase  in  the  production  of  C02.  Richet '  has  shown  that  in  the  same 
Bpecies  the  quantity  of  C02  exhaled  (indicating  the  intensity  of  the  oxidation- 
processes)  is  inversely  proportional  to  the  body-weight  and  is  directly  propor- 
tional to  the  body-surface.  The  following  figures  illustrate  these  important 
facts : 


Mean  Body-weight 
(kilograms). 

CO._,  per  Kilogram 

~  per  Hour 

(grams). 

Body-surface 

(sq.  cm.). 

C02  per  100 
sq.  cm. 
(grams). 

24 
11.5 
6.5 

3.-1 

1.026 

1.380 
1.624 
1.964 

9296 
5656 
3940 
2341 

2.65 
2.81 
2.69 
2.71 

Thus,  an  animal  weighing  24  kilograms  will  give  off  1.026  grams  of  COz 
per  hour  for  each  kilogram  of  body-weight,  while  one  weighing  3.1  kilograms 
Mill  give  off  1.964  grams,  or  nearly  twice  as  much,  for  equal  increments  of 
weight.  It  will  be  observed  by  comparing  the  quantity  of  C02  and  the  body- 
surface  that  for  each  100  square  centimeters  of  surface  the  elimination  is  about 
the  same. 

Age  exercises  an  important  influence.  Until  full  growth  respiratory  activity 
is  higher  than  in  middle  life,  and  in  middle  life  it  is  higher  than  in  old  age. 
In  children  the  absolute  quantities  of  ()  consumed  and  C02  formed  are  less 
than  in  the  adult,  but  in  relation  to  body-weight  they  are  about  twice  as  much. 
During  middle  life  respiratory  activity  is  about  one-sixth  higher  than  during 
old  age.  In  the  young  the  quantity  of  O  in  relation  to  C02  is  higher  than  in 
the  adult. 

Andral  and  Gavarret  have  shown,  in  investigations  relative  to  sex,  that 
after  the  eighth  year  males  give  off  from  one-third  to  one-half  more  C02  than 
females,  the  difference  being  most  pronounced  at  puberty.  During  pregnancy 
and  after  the  menopause  the  relative  quantity  of  C()2  rises. 

The  influence  of  constitution  is  manifest  by  a  greater  intensity  of  respi- 
ratory activity  in  the  robusf  than  in  the  weak,  other  conditions  being  the 
same. 

The  rate  (nnl  depth  of  //"  respiratory  movements  do  not  appreciably  affect 
the  volumes  of  O  and  C()2  interchanged,  although  the  removal  of  C02  is  facili- 
tated by  an  increase  of  the  volume  of  air  respired,  because  of  the  better  ven- 
tilation of  the  lungs.  An  increase  in  the  rate,  the  depth  remaining  constant, 
increases  the  volume  of  air  respired  and  the  absolute  quantity  of  C02  given 
off,  but  the  quantity  of  C02  in  relation  to  the  total  volume  of  air  is  less.  If 
1  Archives  de  Physiologie  normale  </  ■pathologique,  t.  22,  pp.  17-30. 


RESPIRATION.  431 

the  rate  remain  constant  and  the  depth  be  increased,  similar  results  are 
obtained. 

The  quantity  of  C02  eliminated  during  slow,  deep  respirations  is  larger 
than  during  rapid,  shallow  respirations. 

The  diurnal  variations  are  in  accord  with  the  changes  in  the  respiratory 
rate — rising  after  we  awake,  falling  during  the  forenoon,  again  rising  after  the 
mid-day  meal,  again  falling  during  the  afternoon,  increasing  after  the  evening 
meal,  and  falling  to  a  minimum  during  the  night. 

Sunlight  exercises  a  marked  influence,  as  is  proven  by  the  results  obtained 
by  a  number  of  investigators.  In  frogs  the  elimination  of  C02  is  increased 
by  sunlight,  even  after  excision  of  the  lungs.  Fubini  and  Benedicenti,1  in 
experiments  upon  hvbernating  animals,  found  that  the  comparative  quantities 
of  CO,  eliminated  under  the  influence  of  sunlight  and  of  darkness  were  as 
100:93.48.  Fubini  and  Spallitta2  have  also  shown  that  different  colored 
lights  variously  affect  the  output  of  C02  in  different  species. 

Respiratory  activity  is  affected  by  the  character  and  quantity  of  the  food. 
The  following  results,  obtained  by  Pettenkofer  and  Voit,  are  very  instructive  : 

Non-nitrogenous  Nitrogenous 

Fasting.  Mixed  Diet.  Diet  Djet 

O 743  grams.  867  grams.  808  grams.  1083  grams. 

C02 695       "  930       "  839       "  850      " 

It  will  be  observed  that  respiratory  activity  is  lowest  during  fasting,  higher 
when  the  diet  is  non-nitrogenous,  still  higher  when  the  diet  is  mixed,  ano7 
highest  when  the  diet  is  purely  nitrogenous.  The  respiratory  quotient  is 
higher  when  the  diet  is  rich  in  carbohydrates  (p.  437),  while  it  falls  in  propor- 
tion to  the  percentage  of  nitrogenous  food.  Fasting  reduces  the  quotient  con- 
siderably, and  if  coupled  with  inactivity  (hybernation)  causes  it  to  fall  to  a 
minimum. 

During  digestion  the  gaseous  exchange  is  increased,  according  to  Loewy,3 
from  7  to  30  per  cent.  Joylet,  Bergonic,  and  Sigalas  '  obtained  the  following 
averages  of  seven  experiments  on  a  man  weighing  52  kilograms,  the  increase 
of  O  being  about  7  per  cent.,  and  of  C02  about  6  per  cent. : 


Before  food 
After  food 


o. 

CO,. 

259  c.c 

298.4  c.c. 

275   " 

317      " 

The  increase  of  respiratory  activity  during  digestion  may  be  due  to  the 
chemical  processes  involved  in  the  production  of  the  digestive  secretions,  to 
the  oxidation  of  the  products  of  digestion  after  absorption,  or  U>  muscular 
activity  of  the   gastro-intestinal   walls.     Zuntz   and    Mering  '  endeavored  to 

1  MoUschottia  Untersuch.  z.  Natwrl.,  L887,  Bd.  1  I.  S.  623  629. 

2  Ibid.,  L8S6,  Bd.  13,  S.  563. 

3  Archiv  fiir  die  gesammle  Physiologic,  1888,  Bd.  4:'..  S.  515  532. 

*  Complex  rend  us,  1887,  t.  105,  pp.  390,  675. 

*  AvchlV fiir  die  gexftnunte  I'hysiologie,  1883,  ltd.  '.VI,  S.  173-221. 


432  IV    AMERICAN   TEXT-BOOK    OF  PHYSIOLOGY. 

settle  this  point  by  making  three  series  of  experiments :  in  one  they  injected 
certain  readily  oxidizable  substances  into  the  blood;  in  another  the  substances 
were  injected  into  the  stomach;  and  in  another  sulphate  of  sodium  or  other 
purgative  was  given.  When  the  substances  were  injected  into  the  blood,  Zuntz 
and  Mering  found  as  a  general  result  that  the  absorption  of  O  was  not  increased, 
while  the  formation  of  C02  was  slightly  increased  ;  when  injected  into  the  stom- 
ach, no  marked  increase  in  respiratory  activity  occurred  unless  the  substances  were 
given  in  large  quantities.  When,  however,  in  addition  to  the  readily  oxidiz- 
able substances,  a  purgative  was  injected,  or  when  the  purgative  was  given 
alone,  the  absorption  of  O  and  the  elimination  of  0O2  were  considerably  in- 
creased. They  were  therefore  led  to  conclude  that  the  increased  respiratory 
interchange  during  digestion  is  due  chiefly  to  the  muscular  activity  of  the 
intestinal  walls.  Loewy1  has  confirmed  this  conclusion,  and  has  clearly  shown 
that  the  increase  in  respiratory  activity  is  chiefly  related  to  the  intensity  of 
peristalsis,  the  most  marked  increase  being  associated  with  excessive  peristaltic 
activity.  There  can  be  no  reasonable  doubt,  however,  that  a  portion  of  the 
increase  is  due  both  to  glandular  activity  and  to  the  breaking  down  of  the 
absorbed  products  of  digestion. 

The  volumes  of  O  absorbed  and  of  CO,  produced  rise  with  an  increase  of 
body  temperature.  This  fact  has  been  illustrated  by  the  experiments  of 
Pfluger  and  Colasanti  on  guinea-pigs,  in  which  they  found  that  the  quantity 
of  O  absorbed  at  a  body  temperature  of  37.1°  was  948.17  cubic  centimeters; 
at  38.5°,  1137.3  cubic  centimeters;  at  39.7°,  1242.6  cubic  centimeters,  per 
kilo  per  hour.  Similar  results  have  been  obtained  by  other  investigators  in 
experiments  both  upon  the  human  subject  and  upon  the  lower  animals  under 
the  pathological  conditions  of  fever.  A  fall  of  body  temperature  is  accom- 
panied by  a  decrease  in  the  intensity  of  respiration,  unless  the  fall  is  accom- 
panied by  muscular  excitement,  such  as  shivering.  Speck2  lias  seen  shiver- 
ing cause  the  consumption  of  O  to  rise  from  302  to  496  cubic  centimeters, 
and  the  exhalation  of  CCX,  from  287  to  439  cubic  centimeters.  The  primary 
and  fundamental  effect  of  lowering  the  body  temperature  is  to  diminish  respi- 
ratory activity,  but  this  may  be  more  than  compensated  for  by  involuntary 
or  voluntary  excitement  of  the  muscles  (p.  433;  see  also  Tissue-respiration). 

The  effects  of  cricrinil  fem/icrature  upon  warm-  and  cold-blooded  animals 
are  different:  Molesohotl  found  that  frogs  produced  three  times  more  C02  at 
38.7°  than  at  6°,  while  in  warm-blooded  animals  the  opposite  is  the  case — that 
is,  three  times  more  COa  is  formed  at  the  lower  temperature.  The  frog's  tem- 
perature rises  and  falls  with  changes  in  the  temperature  of  the  surroundings, 
while  that  of  warm-blooded  animals  remains  at  a  fairly  constant  standard; 
he  'ee  the  respiratory  intensity  in  the  frog  increases  with  the  rise  of  external 
temperature,  while  in  warm-blooded  animals  it  decreases,  owing  to  diminished 
heat-production.  But  in  warm-blooded  animals  the  alterations  in  respiratory 
activity  caused  by  changes  of  external  temperature  are  not  always  in  inverse 
relation.  Thus,  Voit  has  shown,  as  a  resull  of  studies  in  man,  that  the  exhala- 
1  Lor.  tit.  '  Deutsche*  Archiv  /.  klin,  Med.,  1889,  Bd.  33,  S.  375,  424. 


RE8PIRA  '/'/ox  133 

tion  of  C02  diminishes  with  the  rise  of  external  temperature  from  4.4°  until 

the  temperature  reaches  14.3°,  when  it  rises  slowly.  Those  results  have  been 
substantiated  by  the  more  recent  investigations  of  Page,1  who  found  in  experi- 
ments on  dogs  that  the  discharge  of  C02  was  at  a  minimum  at  about  2o°  ; 
that  below  this  temperature  the  quantity  increased  as  the  temperature  fell; 
ami  that  above  this  temperature  the  discharge  increased,  and  became  greatly 
augmented  at  temperatures  of  40°  to  42°.  At  the  latter  temperatures  the 
increase  may  reach  Sh  times  the  normal,  but  the  bodily  temperature  is  also 
increased.  If  the  elimination  of  C02  at  23°  to  24°  be  represented  by  100  as 
a  standard,  at  13°  it  will  be  about  128;  at  10°,  141  ;  and  at  8°,  177.  The 
researches  of  Speck,2  of  Loewy,3  of  Quinquaud,4  and  of  Johansson 5  all  show 
that  external  cold  increases  respiratory  activity,  chiefly  or  solely  by  causing 
involuntary  muscular  excitement  (shivering).  If  shivering  and  other  forms 
of  muscular  activity  be  absent,  the  exchange  of  O  and  C02  is  unaffected  or  even 
diminished,  but  when  present  the  increase  of  respiratory  activity  may  amount 
to  100  per  cent,  notwithstanding  a  fall  of  bodily  temperature  below  the  normal. 
Muscular  activity  is  one  of  the  most  important  of  all  the  circumstances 
affecting  the  quantities  of  O  and  C02  exchanged.  Involuntary  excitement, 
such  as  shivering,  may  of  itself  double  the  consumption  of  O  and  increase 
two  and  a  half  times  the  elimination  of  C02,  but  volitional  muscular  effort 
may  increase  the  interchange  even  beyond  these  limits.  Hirn,  in  investiga- 
tions on  four  men,  noted  during  rest  an  hourly  absorption  of  30.2  grams  of 
O,  and  during  work  120.9  grams;  and  Pettenkofer  and  Voit,  in  similar 
studies,  found  an  increase  of  O  from  867  grams  during  rest  to  1006  grams 
during  moderate  work,  and  from  930  grams  of  C02  to  1137  grams.  In 
experiments  on  the  horse  Zuntz  and  Lehmann6  obtained  the  following 
results,  which  show  to  what  a  marked  extent  the  respiratory  interchange 
may  be  increased  by  muscular  activity  : 


Liters  per  Minute. 

COj 

o 


O.  CO, 


Kesting 1.722  1.570  0.92 

Walking 4.766  4.342  0.90 

Trotting     8.093  7.516  <>.'.':; 

Speck7  has  added  some  interesting  facts  to  our  knowledge  of  the  effects  of 
muscular  activity  on  the  respiratory  interchange.  Thus,  he  found  that  the 
increase  of  O  and  CG2  reaches  a  maximum  before  exertion  reaches  its  maxi- 
mum ;  that  the  increase  for  the  same  amount  of  work  can  be  varied  by  chang- 
ing the  position  of  the  body;  that  if  a  given  amount  of  work  be  divided  into 
two  equal  parts,  the  increase  of  respiratory  activity  during  the  first  period  is 
greater  than  during  the  second  ;  that   the  greater  the  increase  of  ( '<  >,.  the   less, 

i  Journal  of  Physiology,  1879-80,  vol.  2,  p.  228.  2  Lor.  at. 

1  Archiv  fur  die  gesammte  Physiologie,  1890,  Bd.  46,  S.  189-224. 
*  Oompies  rendvs,  1887,  t.  104,  pp.  1542  1544 

5  Skandinavisches  Archiv  fur  Physiologie,  1897,  Bd.  7,  S.  123-177. 

6  Journal  of  Physiology,  1890,  vol.  2,  p.  396. 

7  Deutsche*  Archiv  f.  Win.  Med.,  1889,  Bd.  45,  S.  460-528. 

Vol.  I.— 28 


434  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

proportionately,  is  the  increase  of  O,  so  that  the  respiratory  quotient  rises 
more  and  more,  and  to  such  an  extent  that  the  C02  contains  more  O  than  is  at 
the  time  absorbed;  and  that  the  quantity  of  air  respired  is  so  intimately  related 
to  the  amount  of  C02  given  off  that  he  regards  the  quantity  of  this  gas 
formed  as  the  regulator,  as  it  were,  of  the  degree  of  activity  of  the  respiratory 
movements. 

Griiber1  states  that  while  respiratory  activity  is  proportional  to  the  inten- 
sity of  muscular  activity,  "training"  diminishes  the  quantity  of  C02  given 
oil*  for  the  same  amount  of  work.  Thus,  taking  1  as  a  standard  of  the 
amount  of  C02  eliminated  during  rest,  he  obtained  the  following  ratios  in  two 
series  of  observations : 

Climbing  hills         Climbing  hills 
Resting.  Walking.  when  not  used         when  used  to 

to  it.  it. 

Fire!  series 1  1.89  4.1  3.3 

.Second  series _1_  L75  3^05  2A2 

Mean 1  1.82  3.57  2.86 

Training  therefore  reduces  the  output  about  20  per  cent. 

The  elimination  of  C02  is  about  one-fifth  less  during  sleep  than  while 
awake  and  quiet ;  from  one-fifth  to  one-half  greater  during  ordinary  exertion  ; 
from  two  to  two  and  a  half  times  greater  during  violent  exercise;  and  about 
three  times  greater  during  tetanus. 

During  hybernation  the  absorption  of  O  falls  to  -^j  and  the  elimination  of 
( '( ).,  to  -^  of  the  normal  for  the  period  of  activity  (Valentine).  Relatively 
more  O  is  absorbed  than  C02  given  off,  hence  the  respiratory  quotient  falls, 
reaching  as  low  as  0.50  to  0.75. 

A  diminution  of  the  barometric  pressure  increases  the  respiration-rate  and 
the  volume  of  air  respired,  but  both  Mosso  and  Marcet  have  shown  that  if 
allowance-  be  made  for  the  increase  of  volume  of  the  air  at  the  lower  pressure, 
the  actual  volume  respired  is  less.  Conversely,  an  increase  of  pressure  lowers 
the  rate  and  the  volume  of  air  respired.  Extremes  of  pressure  severely  affect 
the  respiratory  and  other  functions  (p.  451). 

The  integrity  of  the  nervous  apparatus  which  governs  the  metabolic  pro- 
cesses  in  the  tissues  is  obviously  of  fundamental  importance.  If  the  efferent 
nerve-fibres  of  a  muscle  be  cut,  the  interchange  of  O  and  C02  at  once  sinks, 
as  illustrated  by  the  following  results  obtained  by  Zuntz : 

O  consumed.  C02  given  off. 

Before  section 13.2    c.c.  14.4  c.c. 

After  section 10.45  c.c.  10-1  c.c. 

After  section    less] 2.75  c.c.  4.3  cc. 

The  consumption  of  O  was  therefore  lessened  about  20  per  cent.,  and  the 
formation   of  C02  about    30    per  cent. 

After  secti< f  the  spinal  cord  in  the  dorsal   region  Quinquaud  2  obtained 

1  Zeitschrifi  f.  Biokgie,  1891,  Bd.  28,  S.  466-491. 
'  Compt.  rend.  Soc.  Bioloyie,  1887,  pp.  340 -342. 


BESPIBA  TION.  \  • !  5 

similar  results.  Before  the  section  the  blood  in  the  crural  vein  contained  9.5 
per  cent,  of  O  and  60  per  cent,  of  C02;  after  section  it  contained  13.5  per 
cent,  of  O  and  40  per  cent,  of  C02,  showing  that  the  consumption  of  O  by 
the  tissues  and  the  formation  of  C02  were  considerably  lessened.  After  de- 
struction of  the  spinal  cord  respiratory  activity  falls  to  a  minimum. 

The  study  of  the  effects  of  alterations  in  the  composition  of  the  inspired  air 
on  the  absorption  of  O  and  the  elimination  of  C02  are  of  great  importance. 
Nitrogen  is  merely  a  mechanical  diluent  of  the  inspired  air,  and  may  be 
replaced  by  H  or  by  other  inert  gas,  so  that  alterations  in  its  percentage  do 
not,  per  se,  affect  the  respiratory  phenomena ;  but  changes  in  the  percentages 
of  O  and  C02  may  cause  marked  disturbances  both  of  the  respiratory  move- 
ments and  of  the  gaseous  interchange. 

When  the  percentage  of  O  in  the  inspired  air  is  increased  up  to  40  volumes 
per  cent.,  Bert  found  that  there  occurred  an  increase  in  the  quantity  absorbed, 
and  both  Speck  and  Fredericq  have  noted  merely  a  transient  increase  under 
similar  circumstances;  but  the  results  of  most  experimenters,  on  the  contrary, 
seem  to  show  quite  conclusively  that  an  increase  of  the  per  cent,  of  O  above 
the  normal  does  not  affect  the  quantity  absorbed.  Lukjanow1  in  a  large 
number  of  experiments  could  not  detect  any  increase,  and  Saint-Martin,2  in 
researches  on  guinea-pigs  and  rats  with  an  atmosphere  containing  from  20  to 
75  volumes  per  cent,  of  O,  noted  the  same  result.  Even  in  an  atmosphere  of 
pure  O  animals  breathe  as  though  they  were  respiring  normal  atmospheric  air. 

A  decrease  in  the  percentage  of  O  is  without  influence  until  the  proportion 
falls  below  13  volumes  per  cent.  Worm-Miiller  long  ago  showed  that  animals 
breathe  quietly  in  air  containing  14.8  volumes  per  cent,  of  O,  and  that  if  the 
proportion  fell  to  7  volumes  per  cent.,  respiration  became  slow,  deep,  and  diffi- 
cult; with  4.5  volumes  per  cent,  marked  dyspnoea  occurred;  and  when  there 
was  but  3  volumes  per  cent,  asphyxia  rapidly  supervened.  The  more  remit 
results  of  Speck3  not  only  confirm  the  main  facts  of  Worm-Midler's  observa- 
tions, but  furnish  other  important  data.  He  has  shown  that  when  the 
atmosphere  contains  13  volumes  per  cent,  of  (),  respiration  is  quiet  and  the 
quantity  of  O  absorbed  is  but  slightly,  if  at  all,  diminished,  and  that  even 
when  the  proportion  falls  to  9.65  volumes  per  cent,  breathing  is  carried  mi  for 
a  long  time  without  inconvenience,  the  amount  of  ()  absorbed,  however,  being 
diminished.  He  shows,  moreover,  that  when  the  volume  of  0  in  the  atmo- 
sphere falls  to  s  per  cent,  the  respiratory  movements  are  deep  and  are  but 
slightly  accelerated,  the  quantity  of  O  absorbed  being  very  much  diminished, 
and  that  the  animal  subjected  to  such  an  atmosphere  succumbs  in  a  few 
moments.  The  quantity  of  O  taken  into  the  lungs  falls  proportionately  with 
the  diminution  of  O  in  the  inspired  air  until  the  reduction  reaches  11.26  vol- 
umes per  cent.,  but  further  diminution  is  compensated  for  by  an  Increase  in 
the  volume  of  air  respired.     As  the  volume  per  cent.  <-i   0  in  the  inspired  air 

1  Zeitschrift  f.  physiolog.  Chemie,  1883-1884,  Bd.  8,  S.  313-335. 

•-'  Compt.  rend.,  1885,  t.  98,  pp.  241-243. 

*  Zeitschrift  f.  Mm.  Med.,  1887,  Bd.  12,  S.  117  532. 


436  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

diminishes  the  relative  percentage  of  O  absorbed  increases,  and  this  continues 

until  the  volume  in  the  inspired  air  is  reduced  to  11.26  per  cent.,  27  per  cent, 
of  which  is  absorbed;  below  this  point  no  further  increase  of  absorption 
occurs.  As  the  quantity  of  O  absorbed  is  reduced  the  respiratory  quotient 
becomes  greater,  and  may  reach  as  high  as  2.218. 

When  the  quantity  of  O  remains  al  the  normal  standard  and  the  percentage 
of  C02  is  much  increased,  the  elimination  of  the  latter  is  interfered  with  ;  and 
Pfluger  has  shown  thai  if  the  percentage  of  C02  be  high,  dyspnoea  ensues, 
notwithstanding  the  fact  that  the  blood  contains  a  normal  amount  of  O. 
When  air  contains  3  to  4  volumes  per  cent,  of  C02,  the  quantity  of  C02 
given  off  is  diminished  about  one-half.  Speck1  and  others  have  found  that 
the  elimination  of  CG2  during  a  given  period  may  be  independent  of  both 
the  percentage  of  O  in  the  inspired  air  and  the  quantity  absorbed.  An  atmo- 
sphere containing  10  volumes  per  cent,  of  C02  is  generally  believed  to  be  toxic, 
but  Wilson's2  investigations  show  that  air  having  even  as  much  as  25  to  30 
volumes  per  cent,  may  be  inhaled  with  impunity.  It  is  quite  probable  that 
in  those  cases  in  which  small  percentages  of  C02  in  the  inspired  air  have 
proven  poisonous  the  gases  were  contaminated  with  CO  (carbon  monoxide). 
Respiration  of  an  atmosphere  of  pure  0O2  is  followed  within  two  or  three 
minutes  by  death. 

Worm-Muller  found  that  when  animals  breathe  atmospheric  air  in  a  large 
closed  chamber  O  disappears  and  C02  accumulates,  and  death  finally  occurs, 
not  from  a  lack  of  O,  but  from  the  increase  of  C02,  as  is  shown  by  the  fact 
that  at  the  time  of  death  the  quantity  of  O  in  the  air  is  sufficient  to  sustain 
life.  He  has  shown  that  animals  placed  in  a  closed  atmosphere  of  pure  O  die 
from  an  accumulation  of  ('( )_,  in  the  blood,  rabbits  succumbing  after  the  reten- 
tion of  a  volume  of  CO,  equal  to  one-half  the  volume  of  the  body,  and  at  a 
time  when  the  atmosphere  contained  as  much  as  50  volumes  per  cent,  of  O. 

The  dyspnoea  occurring  in  an  animal  confined  in  an  air-tight  chamber  of 
small  size  is  due  to  the  lack  of  O,  nearly  all  of  the  gas  being  absorbed  before 
the  animal  dies,  li'  a  cold-blooded  animal,  such  as  a  frog,  be  similarly  ex- 
posed, the  attraction  of  haemoglobin  for  O  is  so  strong  that  almost  every  par- 
ticle of  gas  will  pass  into  the  blood  long  before  death  occurs;  and  even  after 
the  total  disappearance  of  O  the  elimination  of  C02  is  said  to  continue  at  the 
normal  rate. 

Animals  placed  in  a  confined  space  become  accustomed,  as  it  were,  to  the 
vitiated  air,  and  survive  longer  than  a  fresh  animal  suddenly  thrust  into  the 
poisonous  atmosphere. 

The  Respiratory  Quotient. — The  relation  between  the  quantities  of  O 
absorbed  and  C02  given  off  during  a  given  period  is  expressed  as  the  respira- 
tory quotient  The  air  during  its  sojourn  in  the  lungs  loses  4.78  volumes  per 
cent,  of  O  and  acquires  4.34  volume-  per  cent,  of  C02,  hence  the  respiratory 

quotient    is    — ~      ''^  =  0.901.     This    quotient    is   subject   to  considerable 

1  Loc.  cit.  2  American  Journ.  Pharmacy,  1893,  p.  561. 


RESPIRA  TION.  437 

variations  not   only  in  different  species,  but   in   different   individuals   under 
varied  circumstances.     The  chief  reasons  for  the  differences  are : 

First,  the  production  of  C02  is  in  a  measure  independent  of  the  O  absorbed, 
as  is  proven  by  the  records  of  various  investigators,  showing  that  C02  results 
both  from  oxidation-processes  and  from  intramolecular  splitting  (analogous  to 
fermentation-processes)  which  may  be  entirely  independent  of  each  other; 
that  the  quantity  of  0O2  eliminated  may  continue  under  certain  circumstances 
at  the  normal  standard  even  after  the  absorption  of  O  has  ceased ;  and  that 
the  quantity  of  O  contained  in  the  C02  eliminated  during  a  given  time  may 
be  larger  than  the  actual  quantity  absorbed.  This  may  be  understood  in  a 
general  way  when  we  remember  that  the  CC)2  formed  in  the  body  is  not  the 
result  of  an  immediate  oxidation  of  the  carbon-containing  material  of  the 
body ;  on  the  contrary,  some  of  the  O  absorbed  may  be  stored,  as  it  were,  in 
the  form  of  complex  compounds,  which  at  some  later  time  may  undergo  disin- 
tegration, with  the  formation  of  C02 ;  or  the  complex  materials  introduced  as 
food  may  undergo  a  similar  disintegration  and  splitting  of  the  molecules,  with 
the  formation  of  C02  independently  of  the  direct  action  of  the  O  upon  them. 
Second,  a  larger  quantity  of  0O2  is  formed  per  unit  of  oxygen  from  the 
disintegration  of  certain  substances  than  from  others,  consequently  the  quotient 
must  be  affected  by  the  nature  of  the  substances  broken  down.  Thus,  in  the 
formation  of  C02  from  carbohydrates  all  of  the  O  consumed  in  the  disinte- 
gration of  the  molecules  is  used  in  forming  C02,  the  H  already  having  suffi- 
cient O  to  satisfy  it ;  but  in  the  case  of  fats  and  proteids  a  portion  of  the  O 
is  utilized  in  the  oxidation  of  H  to  form  H20.  6  molecules  of  O  will  oxidize 
1  molecule  of  grape-sugar  (C6H1206)  into  6C02  +  6H20 ;  hence  the  quotient  is 

n  2  =1.     In  regard  to  fat,  if  we  take  olein,  C3H5  (C^H^O^,  as  an  ex- 
ample, 80  molecules  of  O  are  required  to  reduce  each  molecule  of  the  fat  to 

5  7  CO 
57  molecules  of  C02  and  52  molecules  of  H20  ;  hence  the  quotient  is  - Qnr.   2 

80  (J2 

=  0.712.     In  the  disintegration  of  proteid  only  a  part  of  the  C  is  oxidized 

into  C02,  the  remainder  being  eliminated  as  a  constituent  of  various  complex 

effete  bodies;  but  it  is  estimated  that  the  quotient  for  proteids  (albumin)  is 

from  0.75  to  0.81,  depending  upon  the  completeness  of  disintegration. 

The  respiratory  quotient  varies  with  species,  food,  age,  the  time  of  day, 
internal  and  external  temperature,  muscular  activity,  the  composition  of  the 
inspired  air,  etc. 

In  regai'd  to  species,  the  quotient  is  higher  in  warm-blooded  (0.70  to  LOO) 
than  in  cold-blooded  animals  (0.G5  to  0.75) ;  in  herbivora  (0.90  to  1.00)  than 
in  carnivora  (0.75  to  0.80) ;  and  in  omnivora  (0.80  to  0.90)  than  in  carnivora, 
but  lower  than  in  herbivora.  These  differences  are  due  essentially  to  diet, 
herbivora  feeding  largely  upon  carbohydrates,  omnivora  using  carbohydrates 
to  a  less  extent,  and  carnivora  practically  not  at  all.  These  observations  are 
substantiated  by  the  fact  that  during  lasting,  when  the  animal  is  feeding  upon 
its  own  tissues,  the  respiratory  quotient  in  all  species  is  the  same  (0.7  to  0.75). 


138  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

The  quotient  is  lowered  by  an  animal  diet  and  increased  by  a  vegetable  diet, 
the  ratio  approximating  unity  if  the  diet  be  sufficiently  rich  in  carbohydrates. 
Ilaiuiot  and  Richet l  in  observations  on  man  noted  that  before  feeding  the  quo- 
tient was  0.84  to  0.89;  when  meat  or  fat  was  given  the  consumption  of  O  was 
increased,  but  there  was  no  increase  in  C02,  and  the  quotient  fell  to  0.76  ;  when 
given  potatoes  it  was  ().!»:',  ;  and  when  the  diet  was  of  glucose  it  reached  1.03. 
During  fasting  the  quotient  falls  rapidly.  The  experiments  of  Zuntz  and 
Lehmann  -  show  that  in  dogs  it  falls  as  low  as  0.65  to  0.68  on  the  second  day 
of  lasting,  and  that  on  the  resumption  of  food  it  rises  to  0.73  to  0.81. 

The  influence  of  age  is  manifest  in  the  fact  that  in  children  the  quotient  is 
lower  than  in  the  adult,  more  O  being  absorbed  in  proportion  to  the  0O2  given 
otf  than  after  full  growth  has  been  reached. 

The  quotient  undergoes  a  diurnal  variation.  The  day-time  is  more  favor- 
able than  the  night  for  the  discharge  of  C02,  as  well  as  for  the  absorption  of 
O,  owing  mainly  to  greater  muscular  activity  luring  the  day,  but  the  C02 
is  more  affected  than  theO;  hence  the  respiratory  quotient  is  higher  during 
the  day.  In  the  recent  experiments  by  Saint-Martin3  on  birds,  the  mean  quo- 
tient during  the  day  was  0.83  and  during  the  night  0.72  ;  the  ratio  for  C02 
for  the  day  and  night  was  1  :  0.78,  and  for  O  1  :  0.9.  During  the  night  the 
elimination  of  CC)2  was  diminished  about  20  per  cent.,  while  the  absorption  of 
O  fell  only  about  10  per  cent. 

The  quotient  is  increased  by  a  rise  of  external  temperature.  Thus,  Pfliiger 
and  Finkler  found  in  guinea-pigs  that  the  quotient  was  0.83  at  3.64°  and  0.94 
at  2ii. 21°.  When  the  bodily  temperature  is  increased,  as  in  fever,  the  respira- 
tory quotient  remains  practically  unaltered.  When  the  temperature  falls  below 
the  normal  the  respiratory  quotient  increases. 

Muscular  activity  is  also  an  important  factor.  During  rest  the  consumption 
of  O  by  muscles  is  greater  than  the  production  of  CO,,  while  during  contrac- 
tion the  difference  becomes  less  and  less  in  proportion  to  the  degree  of  activity, 
until  finally  more  0O2  may  be  given  off  than  there  is  O  consumed.  Sczelkow 
found  in  experiments  on  muscles  of  rabbits  at  rest  and  in  tetanus  that  the 
respiratory  quotient  was  decidedly  increased.  A  mean  of  six  experiments 
gives  as  the  quotient  during  rest  0.543  and  during  tetanus  0.933;  in  one-half 
of  the  experiments  it  went  above  1,  and  in  one  instance  to  1.13. 

During  sleep  the  output  of  C02  is  diminished  more  than  the  consumption 
of  O  (p.  434),  so  that  the  respiratory  quotient  is  less  than  when  awake  and 
quiet. 

During  hybernation  the  quotient  falls  to  a  minimum — in  the  marmot  as  low 
as  '). 49.  This  is  due  chiefly  to  the  more  decided  falling  off  in  the  quantity  of 
( '<  >,.  the  C< ).,  being  reduced  to  J7,  and  the  O  to  only  ^j-;  the  animal,  however, 
i-  not  only  in  a  state  of  muscular  quiet,  but  fasting,  which,  it  will  be  remem- 
bered, i>  an  important  factor  in  lowering  the  quotient. 

1  Com,,i.  rend.,  1888,  t.  106,  pp.  496-498. 
*  Berliner  klin.  Woch.,  1887,  S.  128. 
■'Compi.  rend.,  1887,  t.  L05,  pp.  1124-1128. 


BESPIRA  TION.  I J I '.  I 

When  the  percentage  of  O  in  the  inspired  air  falls  so  low  as  to  cause  marked 
dyspnoea,  the  respiratory  quotient  rapidly  rises.  This  is  owing  on  the  one 
hand  to  the  diminished  quantity  of  O  absorbed,  and  on  the  other  hand  to  the 
increased  production  of  CQ2  as  a  consequence  of  excessive  activity  of  the 
muscles  of  respiration.  Speck  (p.  435)  found  that  when  the  proportion  of  0 
was  very  low  the  quotient  rose  as  high  as  2.258. 

E.  Principles  op  Ventilation. 

Breathing  within  a  confined  space,  as  in  a  small  unventilated  room  or  in  a 
large  room  in  which  a  considerable  number  of  persons  are  assembled,  causes 
a  gradual  diminution  in  the  quantity  of  O  and  an  accumulation  of  CO.,,  moist- 
ure, and  organic  matter.  In  regard  to  O,  even  in  the  worst  ventilated  rooms 
the  atmosphere  seldom  contains  as  little  as  15  volumes  per  cent,,  which  is  suffi- 
cient to  permit  of  undisturbed  respiration.  When  the  proportion  of  C02 
exceeds  0.07  volume  per  cent,  the  air  becomes  disagreeable,  close,  and  stuffy — 
offensive  characters  which  are  due  neither  to  the  increase  of  C02  nor  to  a 
deficiency  of  O,  but  to  the  presence  of  odorous  principles  given  off  chiefly  by 
the  body  and  clothing.  Air  from  which  this  organic  exhalation  is  absent 
may  contain  considerably  more  C02  without  causing  any  unpleasant  effects. 
In  well-ventilated  rooms  the  proportion  of  C02  does  not  exceed  0.05  to  0.07 
volume  per  cent. ;  in  badly-ventilated  rooms  it  may  reach  0.25  to  0.30 
volume  per  cent.  ;  while  when  a  large  number  of  individuals  are  crowded 
together,  as  in  lecture-rooms,  it  may  be  as  high  as  0.70  to  0.80  volume  per 
cent.  This  vitiation  is  further  increased  by  the  burning  of  gas  or  oil,  150 
liters  of  ordinary  coal-gas  (enough  to  supply  a  large  burner  for  about  an 
hour)  consuming  all  the  O  in  120O  liters  of  air,  or  as  much  ()  as  is  required 
by  the  average  individual  in  eight  hours,  besides  loading  the  air  with  various 
deleterious  products  of  combustion. 

While  the  accumulation  of  C02  even  in  the  worst  ventilated  rooms  is  not 
in  itself  pernicious,  its  percentage  is  a  practical  working  index  of  the  degree 
of  vitiation.  It  has  long  been  recognized  that  the  atmosphere  of  crowded, 
badly-ventilated  rooms  gives  rise  to  discomfort,  and  by  sonic  the  expired  air 
has  been  erroneously  asserted  to  be  toxic.  Tims  Brown-S6quard  and  d'Ar- 
sonval  condensed  the  moisture  of  the  expired  air  and  found  thai  from  20  to 
40  cubic  centimeters  would  kill  a  guinea-pig;  but  their  results  have  been 
contradicted  positively  by  Dastre"  and  Love.  Lehmann,  Geyer,  and  others. 
The  vitiation  of  the  air  of  badly-ventilated  rooms  cannot  be  said  to  be  due  to 
any  particular  poison,  but  to  an  accumulation  of  odorous  principles  arising 
from  uncleanly  bodies,  clothes,  and  surroundings,  and  also  to  an  accumula- 
tion of  C02,  and  to  a  deficiency  of  O  in  extreme  instances. 

The  quantity  of  fresh  air  required  during  a  given  period  depends  upon  the 
size  of  the  individual,  the  degree  of  activity,  and  the  size  of  the  air-space. 
Assuming  that  an  individual  eliminates  900  grams,  or  158  liters,  of  C02  per 
diem,  and  that  the  percentage  of  C02  is  to  be  kept  at  a  standard  not  exceeding 


440  AN   AMERICAN    TEXT-HOOK    OF  PHYSIOLOGY. 

0.07  volume  percent.,  there  would  be  required  at  least  1,440,000  liters  of 
fresh  air  during  twenty-four  hours,  or  about  60,000  liters  (2000  cubic  feet)  per 
hour.  All  circumstances,  such  as  muscular  activity,  which  increase  the  output 
of  C02  augment  the  demand  for  fresh  air.  When  confined  in  rooms,  every 
person  should  have  an  air-space  equal  to  about  28,000  liters,  or  1000  cubic 
feet,  the  floor-space  should  not  be  less  than  ^  of  the  cubic  capacity  of  the 
room,  and  the  air  should  be  renewed  as  often  as  twice  an  hour.  In  lecture- 
rooms,  school-rooms,  etc.  the  air-space  per  individual  is  usually  very  small,  so 
that  the  renewal  must  be  more  frequent  and  in  proportion  to  the  limitation  of 
space  per  individual. 

Ventilation  i>  accomplished  by  natural  and  artificial  means.  The  forces  of 
the  wind,  the  differences  in  temperature  within  and  without  the  building,  the 
natural  diffusion  of  gases  owing  to  variations  in  composition,  etc.,  all  cause 
more  or  less  circulation.  Artificial  ventilation  is  effected  by  the  use  of  proper 
appliances  for  the  forced  introduction  of  air  into  and  expulsion  from  apartments. 

F.  The  Effects  of  the  Respiration  of  Various  Gases. 

The  respiration  of  pure  ()  takes  place  without  disturbance  of  the  respira- 
tory processes.  Lorrain  Smith1  has  shown  that  O  at  the  tension  of  the 
atmosphere  stimulates  the  Lung-cells  to  active  absorption,  at  a  higher  tension 
acts  as  an  irritant,  or  pathological  stimulant,  and  produces  inflammation. 
Dyspnoea  is  developed  when  the  inspired  air  contains  less  than  13  volumes 
per  cent.  (p.  435).  Respiration  of  pure  COa  (p.  436)  is  fatal  within  two 
or  three  minutes,  but  an  atmosphere  containing  as  much  as  25  to  30  per 
cent,  may  be  respired  for  a  few  minutes  without  ill  effect  (p.  436).  Nitrogen, 
hydrogen,  and  carburetted  hydrogen  (CH4)  may  be  inhaled  with  impunity  if 
they  contain  not  less  than  13  volumes  per  cent,  of  O.  The  respiration  of 
nitrous  oxide  or  of  air  containing  much  ozone  rapidly  produces  aiuesthesia, 
unconsciousness,  and  death.  Carbon  monoxide  (CO)  and  cyanogen  are  decid- 
edly toxic,  combining  with  haemoglobin  and  displacing  oxygen.  Sulphuretted 
hydrogen,  phosphoretted  hydrogen,  arseniuretted  hydrogen,  and  antimoniu- 
retted  hydrogen  are  all  poisonous  and  are  all  destructive  to  haemoglobin.  An 
atmosphere  containing  0.4  volume  per  cent,  of  sulphuretted  hydrogen  is  said 
to  be  toxic  Air  containing  2  volumes  per  cent,  of  CO  (carbon  monoxide)  is 
quickly  fatal.  Certain  gases  and  vapors — as,  for  instance,  ammonia,  chlorine, 
bromine,  ozone,  etc. — produce  serious  irritation  of  the  respiratory  passages,  and 
may  in  this  way  cause  death. 

G.  Effects  of  the  Gaseous  Composition  of  the  Blood   on  the 
Respiratory  Movements. 

Certain  terms  are  employed  to  express  peculiarities  in  the  respiratory  phe- 
nomena:   Ewpnoea  is  normal,  quiet,  and  easy  breathing.     J yy/ma  is  a  suspen- 
sion of  the  respiratory  movements.      Hyperpnoea   is  a  condition  of  increased 
1  Journal  of  Physiology,  1899,  vol.  24,  |>.  19. 


RESPIRA  TIOX.  441 

respiratory  activity.  Polypncea}  thermopolypncea,  and  heat-dyspnoea  are  forms 
of  hyperpnoea  duo  to  heating  the  blood  or  the  skin.  Dyspnoea  is  distinguished 
by  deep  and  labored  breathing;  the  respiratory  rate  is  usually  less  than  the 
normal,  but  in  some  forms  it  may  be  higher.  Asphyxia  (suffocation)  is  cha- 
racterized by  convulsive  respirations  which  arc  followed  in  the  final  stage  by 
infrequent,  feeble,  and  shallow  respirations. 

Eupnoea  is  the  condition  of  respiration  observed  during  bodily  and  mental 
quiet,  the  quantities  of  O  and  C02  in  the  blood  being  within  the  normal  mean 
limits. 

Apncea  may  be  produced  by  rapidly  repeated  respirations  of  atmospheric 
air,  under  which  circumstances  the  respiratory  movements  may  be  arrested  for 
a  period  varying  from  a  few  seconds  to  a  minute  or  more.  This  condition  is 
produced  most  easily  upon  animals  which  have  been  tracheotomized  and  con- 
nected with  an  artificial  respiration  apparatus.  If  under  these  conditions  the 
lungs  are  repeatedly  inflated  with  sufficient  frequency,  and  the  blasts  are  then 
suspended,  the  animal  will  lie  quietly  for  a  certain  period  in  a  condition  of 
apncea.  The  respirations  after  a  time  begin,  usually  with  very  feeble  move- 
ments which  quickly  increase  in  strength  and  depth  to  the  normal  type.  The 
ultimate  cause  of  apncea  is  still  a  mooted  question,  and  the  heretofore  prevalent 
belief  that  it  is  due  to  hyperoxygenation  of  the  blood  is  almost  entirely  dis- 
carded. The  connection  between  the  quantity  of  O  in  the  blood  and  apncea 
is,  however,  suggested  by  several  facts :  thus,  apncea  is  more  marked  after  the 
respiration  of  pure  O  than  after  that  of  atmospheric  air,  ami  less  marked  if  the 
air  is  deficient  in  O;  moreover,  Ewald  states  that  the  arterial  blood  of  apnoeic 
animals  is  saturated  with  O.  These  tacts  naturally  lead  to  the  inference  that  the 
blood  is  surcharged  with  (),  and  that  the  respiratory  movements  are  arrested 
until  the  excess  of  O  is  consumed  or  until  sufficient  COa  accumulates  in  the 
blood  to  excite  respiratory  movements.  But  Head1  has  shown  that  apncea  can 
be  caused  by  the  inflation  of  the  lungs  with  pure  hydrogen  as  well  as  by  infla- 
tion with  air  or  with  pure  O,  although  the  apnoeic  pause  after  the  cessation  of 
the  inflations  is  not  so  long-  or  may  be  absent  altogether;  while  Ewald's  asscr- 
tion  as  to  the  saturation  of  the  blood  with  O  is  contradicted  by  Iloppe-Seyler, 
Gad,  and  others.  The  tact  that  the  apnoeic  pause  exists  lor  a  longer  period 
when  O  is  respired  lends  confirmation  to  Gad's  theory  that  it  is  due  in  part  to 
the  large  amount  of  O  carried  into  and  stored  up,  as  it  were,  in  the  alveoli — 
an  amount  sufficient  to  supply  the  blood  for  a  certain  period  and  thus  to  dis- 
pense with  respiratory  movements,  (tad  found  that  even  when  apnoea  follows 
the  inflation  of  the  lungs  with  air,  the  air  in  the  lungs  contain-  enough  ()  fo 
supply  the  blood  during  the  period  occupied  by  the  blood  in  making  a  com- 
plete circuit  of  the  system.  The  fact,  however,  thai  apmca  can  be  caused 
by  the  inflation  of  the  lungs  by  an  indifferent  gas  such  as  hydrogen,  by 
which  every  particle  of  <)  may  be  driven  from  the  lungs,  certainly  show- 
that  then1  exists  some  important  factor  apart  from  the  Oj  and  this  assump- 
tion receives  support  in  the  observation  that  after  section  of  the  pneumo- 
1  Journal  of  Pin/sin!,,,,,/,  1SS<),  vol.  Id.  pp.  1.  -J7'.». 


442  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

gastric  nerves  (the  channels  for  the  conveyance  of  sensory  impulses  from 
the  lungs  to  the  respiratory  centre)  it  is  very  difficult  to  cause  apnoea  by  in- 
flation of  the  lungs  with  air,  while  if  pure  hydrogen  is  used  violent  dyspnoea 
results.  Tt  seems,  then,  that  apnoea  cannot  be  produced  after  division  of  the 
vagi  unless  there  he  an  accumulation  of  ()  in  the  lungs.  These  facts  suggest 
that  the  frequent  forced  inflations  of  the  lung-  excite  the  pulmonic  peripheries 
of  the  pneumogastric  nerve-,  thus  generating  impulses  which  inhibit  the  inspi- 
ratory discharges  from  the  respiratory  centre.  This  view  receives  further  sup- 
port in  several  facts:  first,  that  the  same  Dumber  of  inflations,  whether  of  pure 
().  of  air,  or  of  H,  causes  apnoea,  the  only  difference  being  the  length  of  the 
apnoeic  pause  after  the  cessation  of  artificial  respiration,  which  pause  lasts  for 
the  longest  period  when  O  is  used,  and  for  the  shortest  period,  or  not  at  all, 
when  II  is  employed;  second,  that  apncea  cannot  be  caused  by  inflation  of  the 
lungs  with  H  if  the  pneumogastric  nerves  be  previously  divided  ;  third,  that  the 
arrest  of  respiration  which  occurs  during  swallowing  ("  deglutition-apnoea") 
i-  due  to  an  inhibition  of  the  respiratory  centre  by  impulses  generated  in  the 
terminations  of  the  glosso-pharyngeal  nerves  (p.  462).  It  therefore  seems  evi- 
dent that  apncea  may  be  due  to  either  gaseous  or  mechanical  factors,  or  to  both, 
the  former  being  effective,  not  because  of  the  blood  being  saturated  with  O, 
but  because  of  the  increased  amount  of  O  in  the  alveoli — a  quantity  sufficient 
for  a  time  to  aerate  the  blood  ;  while  the  mechanical  factors  give  rise  to  inhibi- 
tory impulses  which  suspend  for  a  longer  or  shorter  period  the  rhythmical 
inspiratory  discharges  from  the  respiratory  centre,  doubtless  by  depressing  the 
irritability  of  this  centre  (p.  455).  From  the  experiment  quoted  it  seems  that 
the  first  of  these  factors  may  alone  be  sufficient  to  cause  apncea,  but  that  apncea 
is  more  easily  produced,  and  lasts  longer,  when  both  factors  act  together,  as  is 
usually  the  case. 

The  form  of  hyperpncea  due  to  museular  activity  is  owing  to  the  action 
upon  the  respiratory  centre  of  certain  substances  which  are  formed  in  the 
muscles  during  contraction  and  are  given  to  the  blood.  Muscular  activity, 
as  is  well  known,  is  accompanied  by  an  increase  in  the  rate  and  depth  of  the 
respiratory  movements,  and  when  the  exercise  is  violent  more  or  less  marked 
dyspnoea  may  occur.  Some  physiologists  have  been  led  to  the  belief  that  the 
respiratory  centre  is  connected  directly  or  indirectly  with  the  muscles  by 
means  of  afferent  nerve-fibres  which  convey  impulses  to  the  centre  and  thus 
excite  it  to  activity;  while  other-  have  regarded  a  diminution  of  O  and  an 
increase  ofCOa  in  the  blood  a-  the  cause,  the  active  muscles  rapidly  consum- 
ing tin  ()  in  the  blood  and  giving  off  C02  in  great  abundance.  But  Mathieu 
and  I'rbain.  and  (leppert  and  Zunt/..'  have  found  that  the  volumes  percent, 
in  the  blood  of  O  may  be  increased,  and  the  volume  per  cent,  of  C02 decreased, 
during  muscular  activity.  It  i-  probable  that  the  hyperpncea  is  due  to  prod- 
ucts of  muscular  activity  which  are  given  to  the  blood  and  which  act  as 
powerful  excitant-  to  the  respiratory  centre.  The  precise  nature  of  the 
bodies  is  unknown,  but  it  i-  probable  that  they  are  of  an  acid  character,  for 
1  Arehivftlr  du  gesammle  I  .  1 — ,  Bd.  42,  S.  189. 


RESPIRA  TION.  443 

Lehmann1  found  that  there  was  a  distinct  lessening  of  the  alkalinity  of*  the 
blood  after  muscular  exercise.  It  is  likely  that  the  bodies  arc  broken  up  in 
the  system,  because  the  results  of  Loewy's2  investigations  indicate  that  they 
are  not  removed  by  the  kidneys. 

Polypncea,  tiwrmopolyjmoea,  and  heat-dyspnoea  are  due  to  a  direct  excitation 
of  the  respiratory  centres  through  an  increase  of  the  temperature  of  the  blood, 
or  reflexlv  by  excitation  of  the  cutaneous  nerves  by  external  heat.  This  con- 
dition may  be  produced,  as  was  done  by  Goldstein,  by  exposing  the  carotids 
and  placing  them  in  warm  tubes,  thus  heating  the  blood ;  or,  as  was  done  by 
Richet  and  others,  by  subjecting  the  body  to  high  external  heat.  Richet  in 
employing  this  latter  method  found  that  dogs  so  exposed  may  have  a  respira- 
tory rate  as  high  as  400  per  minute.  Ott  records  marked  polypncea  as  a  result 
of  direct  irritation  of  the  tuber  cinereum.  This  form  of  hyperpnoea  is  entirely 
independent  of  the  gaseous  composition  of  the  blood  ;  moreover,  an  animal  in 
heat-dvspncea  cannot  be  rendered  apnoeic,  even  though  the  blood  be  so  thor- 
oughly oxygenated  that  the  venous  blood  is  of  a  bright  arterial   hue. 

Dyspnoea  is  generally  characterized  by  slow,  deep,  and  labored  respiratory 
movements,  although  in  some  instances  the  rate  may  be  increased.  Several 
distinct  forms  are  observed:  "  O-dyspnoea,"  due  to  a  deficiency  of  O; 
"  C02-dyspnoea,"  due  to  an  excess  of  C02  in  the  blood;  and  cardiac  aud 
hemorrhagic  dyspnoeas,  belonging  to  the  O  category. 

Dyspnoeas  due  to  the  gaseous  composition  of  the  blood  may  be  caused  either 
by  a  deficiency  of  O  or  by  an  excess  of  C02,  but  are  generally  due  to  both. 
Dyspnoea  from  a  deficit  of  O  is  observed  when  an  animal  is  placed  within  a 
small  closed  chamber,  or  when  an  indifferent  gas,  such  as  pure  hydrogen  or 
nitrogen,  is  respired.  Under  the  latter  circumstances  dyspnoea  occurs  even 
though  the  quantity  of  C02  in  the  blood  be  below  the  normal.  If,  on  the 
contrary,  the  animal  be  compelled  to  breathe  an  atmosphere  containing  10  vol- 
umes per  cent,  of  CG2,  dyspnoea  occurs,  notwithstanding  an  abundance  of  O 
(p.  436)  both  in  the  air  and  in  the  blood;  indeed,  the  quantity  of  O  in  the 
blood  may  be  above  the  normal.  Fredericq3  in  ingenious  experiments  has 
directly  demonstrated  the  influence  of  the  quantity  of  C02  in  the  blood  upon 
the  respiratory  movements.  He  took  two  rabbits  or  dogs,  A  and  B,  ligated  the 
vertebral  arteries  in  each,  exposed  the  carotids,  and  ligated  one  in  each  animal. 
The  other  carotid  in  each  was  cut,  and  the  peripheral  end  of  the  vessel  of  one 
was  connected  by  means  of  a  cannula  with  the  central  end  of  the  vessel  of  the 
other,  so  that  the  blood  of  animal  a  supplied  the  head  (respiratory  centre)  of 
animal  B,  and  vice  versd.  When  the  trachea  of  animal  A  was  ligated  or  com- 
pressed the  animal  B  showed  signs  of  dyspnoea,  because  its  respiratory  centre 
was  now  supplied  with  the  venous  blood  from  a.  On  the  contrary,  animal  a 
exhibited  quiet  respirations,  almost  apnoeic,  because  its  centre  received  the 
thoroughly  arterialized  blood  from  b,  in  which  the  respiratory  movements  were 
augmented.     In  a  second  series  of  experiments  blood  was  transfused  through 

1  Archivfur  die  gesammte  Physiologic,  L888,  BU  42,  S.  284.  :  Ibid.,  S.  281 

8  Hull.  Acad.  roy.  Mid.  Belgique,  t.  13,  pp.  417-421. 


444  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

the  head:  when  the  blood  was  laden  with  C02  marked  dyspnoea  resulted; 
when  arterial   blood   was  transfused   the  normal   respirations  were  restored. 

While  dyspnoea  may  be  caused  by  the  respiration  of  an  atmosphere  either 
deficient  in  O  ("  O-dyspnoea ")  or  containing  an  excess  of  C02  ("  0O2-dysp- 
Doea  "),  the  phenomena  in  the  two  cases  are  in  certain  respects  different :  When 
an  animal  breathes  pure  N,  thus  causing  O-dyspncea,  the  dyspnoea  is  character- 
ized especially  by  frequent  respiratory  movements  with  vigorous  inspirations, 
whereas  if  the  atmosphere  be  rich  in  O  and  contain  an  excess  of  C02  the 
respirations  are  especially  marked  by  a  slower  rate  and  by  the  depth  and  vigor 
of  the  expirations ',  O-dyspnoea  continues  for  a  longtime  before  death  ensues, 
and  is  more  severe;  in  O-dyspnoea  the  absorption  of  ()  is  diminished,  but  the 
excretion  of  C<  l,  is  practically  unaffected  ;  in  O-dyspnoea  the  attendant  rise  of 
blood-pressure  (p.  447)  is  more  marked  and  lasting;  in  O-dyspnoea  death  is 
I hvii 'dcd  by  violent  motor  disturbances  which  are  absent  in  C<  ),-dvspnoea. 
Blood  poor  in  O  (O-dyspnoea)  affects  chiefly  the  inspiratory  portion  of  the 
respiratory  centre  (p.  457),  while  blood  rich  in  C02  (C02-dvspnoea)  affects 
chiefly  the  expiratory  portion;  hence  in  the  former  the  dyspnoea  is  manifest 
especially  in  an  increase  in  the  frequency  of  the  respirations  (hyperpnoea)  and 
in  the  vigor  of  the  inspirations,  while  in  the  latter  it  is  manifest  in  a  lessened 
rate,  strong  expirations,  and  expiratory  pauses. 

fhe  marked  increase  in  the  depth  of  the  respiratory  movements  in  C02- 
dvspncea  is  not  solely  due  to  the  direct  action  of  C02  upon  the  respiratory 
•  '•litre,  for  Gad  and  Zagari  '  have  shown  that  C02  in  abundance  in  inspired  air 
acts  upon  the  terminations  of  the  sensory  nerves  of  the  larger  bronchi  and 
thus  reflexly  excites  the  respiratory  centre.  In  a  research  on  dogs  these  ob- 
servers opened  the  trachea  and  passed  glass  tubes  through  the  trachea  and  the 
larger  bronchi  to  the  smaller  bronchi.  Before  the  tubes  were  inserted  the 
inhalation  of  C02  caused  a  considerable  deepening  of  the  respiratory  move- 
ments, but  after  the  insertion  of  the  tubes,  by  means  of  which  the  gas  was 
carried  directly  to  the  smaller  bronchi,  the  characteristic  action  of  the  C02  was 
no  longer  observed.  From  the  results  of  these  experiments  we  may  con- 
clude that  the  marked  increase  iu  the  depth  of  the  respiratory  movements 
in  ( '< )_, -dyspnoea  is  due  in  part  to  the  irritation  of  the  sensory  nerve-fibres  of 
the  mucous  membrane  of  the  larger  bronchi. 

(  urdiac  and  hemorrhagic  dyspnoeas  are  chiefly  due  to  the  deficiency  in  the 
supply  of  O — the  former,  to  the  poor  supply  of  blood  due  to  the  enfeebled  action 
of  the  heart  ;  and  the  latter,  both  to  this  and  to  the  reduced  quantity  of  blood 
(haemoglobin).  All  circumstances  which  enfeeble  the  circulation  or  lessen  the 
quantity  of  haemoglobin  therefore  tend  to  cause  dyspnoea  ;  hence  individuals 
with  heart  troubles  or  weakened  by  disease  or  with  certain  forms  of  anaemia 
are  apt  to  suffer  from  dyspnoea  upon  the  least  exertion. 

All  circumstances  which  interfere  with  the  interchange  of  O  and  the 
elimination  of  CO,  in  the  lungs  are  favorable  to  the  production  of  dyspnoea, 

1  Dii  Bois-Reymond'a   Archiv  fur  Physiologie,  1*90,  S.  588. 


RESPIRATION.  445 

as  in  pneumonia,  pulmonary  tuberculosis,  growths  of  the  larnyx,  abdominal 
tumors,  etc.,  especially  so  upon  exertion. 

Asphyxia  is  literally  a  state  of  pulselessness,  but  the  term  is  now  used  to 
express  a  series  of  phenomena  caused  by  the  deprivation  of  air,  as  by  placing 
an  animal  in  a  closed  chamber  of  moderate  size.  These  phenomena  may  be 
divided  into  three  stages:  the  first  is  one  of  hyperpnoea;  the  second,  of 
developing  dyspnoea,  and  finally  of  convulsions;  and  the  third,  of  collapse. 
During  the  first  stage  the  inspiratory  portion  of  the  respiratory  centre 
especially  is  excited,  the  respirations  being  increased  in  frequency  and  depth. 
During  the  second  stage  the  excitation  of  the  expiratory  portion  of  the  respiratory 
centre  is  more  intense  than  that  of  the  inspiratory  portion,  so  that  the  respira- 
tions become  slow  and  deep,  prolonged  and  convulsive,  and  the  movements  of 
inspiration  are  feeble  and  in  striking  contrast  to  the  violent  spasmodic  expira- 
tory efforts.  During  the  third  stage  the  dyspnoea  is  followed  by  general 
exhaustion  ;  the  respirations  are  shallow  and  occur  at  longer  and  longer  inter- 
vals, the  pupils  become  dilated,  the  motor  reflexes  disappear,  consciousness  is 
lost,  the  inspiratory  muscles  contract  spasmodically  with  each  inspiratory  act, 
convulsive  twitches  are  observed  in  the  muscles  of  the  extremities  and  else- 
where, gasping  and  snapping  respiratory  movements  may  be  present,  the  legs 
are  rigidly  outstretched  and  the  head  and  body  are  arched  backward,  feces  and 
urine  are  usually  voided,  respiratory  movements  cease,  and  finally  the  heart 
stops  beating.  During  these  stages  the  circulation  has  undergone  considerable 
disturbances.  During  the  first  and  second  stages  the  blood  has  been  robbed 
of  nearly  all  its  O,  the  gums,  lips,  aud  skin  become  cyanosed,  and,  owing  to  the 
venous  condition  of  the  blood,  the  cardio-inhibitory  centre  has  been  decidedly 
excited,  so  that  the  heart's  contractions  are  rendered  less  frequent;  the  vaso- 
constrictor centre  for  the  same  reason  has  also  been  excited,  causing  a  con- 
striction of  the  capillaries  and  an  increase  of  blood-pressure.  During  the 
third  stage  these  centres  are  depressed  and  finally  are  paralyzed. 

If  asphyxia  be  caused  by  ligating  the  trachea,  the  whole  series  of  events 
covers  a  period  of  four  to  five  minutes,  the  first  stage  lasting  for  about  one 
minute,  the  second  a  little  longer,  and  the  third  from  two  to  three  minutes. 
If  asphyxia  be  produced  gradually,  as  by  placing  an  animal  within  a  relatively 
large  confined  air-space,  death  may  occur  without  the  appearance  of  any  motor 
disturbances  (p.  4.">i>). 

The  heart  usually  continues  beating  feebly  for  several  minutes  after  the 
cessation  of  respiration,  so  that  by  means  of  artificial  respiration  it  is  possible 
to  restore  the  respiratory  movements  and  other  suspended  functions.  After 
death  the  blood  is  very  dark,  almost  black.  The  arteries  are  almost  if  not 
entirely  empty,  while  the  veins  and   lungs  are  engorged. 

Death  from  drowning  occurs  generally  from  the  failure  of  respiration, 
occasionally  from  a  cessation  of  the  heart's  contractions.  It  is  more  difficult 
to  revive  an  animal  asphyxiated  in  this  way  than  one  which,  out  of  water,  has 
simply  been  deprived  of  air  for  the  same  length  of  time.  Dogs  submerged 
for  one  and  a  half  minutes  can   rarely- be  revived,  but  recovery  can  usually  be 


446  AN    AMERICAN    TEXT- BOOK    OF  PHYSIOLOGY. 

accomplished  after  deprivation  of  air,  out  of  water,  for  a  period  four  to 
five  times  longer.  After  ;i  person  has  been  submerged  for  five  minutes  it  is 
extremely  difficult  to  effect    resuscitation. 

H.  Artificial  Respiration. 

Effective  methods  for  maintaining  ventilation  of  the  lungs  are  important 
alike  to  the  experimenter  and  to  the  clinician.  In  the  laboratory  the  usual 
method  is  to  expose  the  trachea,  insert  a  cannula  (Fig.  77),  and  then  period- 
ically force  air  into  the  lungs  by  means  of  a  pair  of  bellows  or  a  pump.  Some 
of  the  forms  of  apparatus  are  very  simple,  while  others  are  complicated.  An 
ordinary  pair  of  bellows  docs  very  well  for  short  experiments,  but  for  longer 

study,  especially  when  it  is  necessary 
that  the  supply  of  air  should  be  uniform, 
the  bellows  are  operated  by  power. 
Some  of  these  instruments  are  so  con- 
structed that  air  is  alternately  forced 
into  and  withdrawn  from  the  lungs. 

Periodical    inflation   of  the  lungs  is 

termed  positive  ventilation ;  the  period- 

1  ■'!.;.  77.— Cannulas  for  dogs  (a)  and  for  cats       ical  withdrawal   of  air  from  the  lungs 

andrabbits<&>'  by  suction  is  negative  ventilation;  and 

alternate  inflation  and  suction   is  compound  ventilation. 

In  practising  artificial  respiration  we  should  imitate  the  normal  rate  and 
depth  of  the  respiratory  movements.  Long-continued  positive  ventilation 
causes  cerebral  anaemia,  a  fall  of  blood-pressure,  and  decrease  of  bodily  tem- 
perature. 

In  human  beings  it  is  not  practicable,  except  under  extraordinary  circum- 
stances, to  inflate  the  lungs  by  the  above  methods,  so  that  we  are  dependent 
upon  such  means  as  will  enable  us  to  expand  and  contract  the  thoracic  cavity 
without  resorting  to  the  knife.  One  method  is  to  place  the  individual  on  his 
back,  the  operator  taking  a  position  on  his  knees  at  the  head,  facing  the  feet. 
The  lower  ribs  are  grasped  by  both  hands  and  the  lower  antero-lateral  portions 
of  the  thorax  are  elevated,  thus  increasing  the  thoracic  capacity,  with  a  conse- 
quent drawing  of  air  into  the  lungs;  the  ribs  and  the  abdominal  muscles  are 
then  pressed  upon  in  imitation  of  expiration.  These  alternate  movements  are 
kept  up  as  long  as  necessary. 

The  following  is  Sylvester's  method  :  "  Place  the  patient  on  the  back,  on  a 
flat  surface  inclined  a  little  upward  from  the  feet;  raise  and  support  the  head 
and  shoulders  on  a  small  firm  cushion  or  folded  article  of  dress  placed  under 
the  shoulder-blades.  Draw  forward  the  patient's  tongue,  and  keep  it  project- 
ing beyond  the  lips;  an  elastic  band  over  the  tongue  and  under  the  chin  will 
answer  this  purpose,  or  a  piece  of  string  or  tape  may  be  tied  around  them,  or 
by  raising  the  lower  jaw  the  teeth  may  be  made  to  retain  the  tongue  in  that 
position.  Remove  all  tight  clothing  from  about  the  neck  and  chest,  especially 
the  braces"  ....  " To  imitate  the  movements  of  breathing :  Standing  at  the 


RESPIRA  TION.  447 

patient's  head,  grasp  the  arms  just  above  the  elbows,  and  draw  the  arms  gently 
and  steadily  upward  above  the  head,  and  keep  them  stretched  upward  for  two 
seconds.  By  this  means  air  is  drawn  into  the  lungs.  Then  turn  down  the 
patient's  arms,  and  press  them  gently  and  firmly  for  two  seconds  against  the 
sides  of  the  chest.  By  this  means  air  is  pressed  out  of  the  lungs.  Repeat 
these  measures  alternately,  deliberately,  and  perseveringly  about  fifteen  times 
in  a  minute,  until  a  spontaneous  effort  to  respire  is  perceived,  immediately 
upon  which  cease  to  imitate  the  movements  of  breathing,  and  proceed  to 
induce  circulation  and  warmth." 

A  new  and  effective  method  has  been  reported  by  Galliano  :  The  patient 
is  placed  in  Sylvester's  position;  the  arms  are  drawn  up  above  and  behind 
the  head,  and  the  wrists  tied.  This  causes  the  thorax  to  be  expanded. 
Respiration  is  accomplished  by  pressing  concentrically  with  the  open  hands 
upon  the  sides  of  the  thorax  and  the  epigastric  region  about  twenty  times  a 
minute.  This  method  is  even  more  effective  if  in  addition  the  jaw  be 
wedged  open,  and  short,  sharp  tractions  of  the  tongue  be  practised  immedi- 
ately preceding  each  pressure  upon  the  thorax.  These  operations  should  be 
continued  for  at  least  one  and  a  half  hours,  if  necessary,  and  aided  by  fric- 
tion, external  heat,  etc.  The  periodical  traction  of  the  tongue  acts  as  a 
strong  excitant  to  the  respiratory  centre. 

I.  The  Effects  of  the  Respiratory  Movements  on  the 

Circulation. 

The  respiratory  movements  are  accompanied  by  marked  changes  in  the  cir- 
culation. If  a  tracing  be  made  of  the  blood-pressure  and  the  pulse  (Fig.  78), 
and  at  the  same  time  the  inspiratory  and  expiratory  movements  be  noted,  it 


Fig.  78.— Blood-pressure  and  pulse  tracing  showing  the  changes  during  Inspiration  (in. >  and  expi- 
ration (ex.). 

will  be  seen  that  the  blood-pressure  begins  to  rise  shortly  after  the  onsel  of 
nspiration,  commonly  after  a  period  occupied  by  one  to  three  heart-beats,  ami 
leaches  a  maximum  after  the  lapse  of  a  similar  brief  interval  after  the  begin- 
ning of  expiration,  when  it  begins  to  fall,  reaching  a  minimum  after  the 
beginning  of  the  next  inspiration.  During  inspiration  the  pulse-rate  ifi  more 
frequent  than  during  expiration  and  the  character  <>f  the  pulse-curve  is  some- 
what different. 

The   Effects   on    Blood-pressure. — The   changes    in    blood-pressure   are 
mechanical  effects  due  to  the  actions  of  the  respiratory  movements.     When  it 


lis  AN    AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

is  remembered  thai  the  lungs  and  the  heart  with  their  great  blood-vessels  are 
placed  within  an  air-tight  cavity,  that  the  lungs  become  inflated  through  the 
aspiratory  action  of  the  muscles  of  inspiration,  and  that  during  inspiration 
intrathoracic  negative  pressure  is  increased,  it  is  easy  to  understand  how  the 
action  which  causes  inflation  of  the  lung-  must  affect  in  like  manner  such 
hollow  elastic  structures  as  the  heart  and  the  great  blood-vessels,  and  thus 
influence  the  circulation.  It  is  obvious,  however,  that  this  influence  must  make 
itself  felt  to  a  more  marked  degree  upon  the  vessels  than  upon  the  heart,  and 
upon  the  flaccid  walls  of  the  vein-  than  upon  the  comparatively  rigid  walls  of 
the  arteries.  Moreover,  the  effects  upon  the  flow  of  blood  through  the  vessels 
entering  and  leaving  the  thoracic  cavity  must  be  different  :  the  inflow  through 
the  veins  must  he  favored,  and  the  outflow  through  the  arteries  hindered;  but 
it  i-  upon  the  flaccid  veins  chiefly  that  the  mechanical  influences  of  inspiration 
are  exerted.  If  the  thoracic  cavity  be  freely  opened,  movements  of  inspiration 
no  longer  cause  an  expansion  of  the  lungs,  nor  is  there  a  tendency  to  distend 
the  heart  and  the  large  blood- vessels;  if,  however,  in  an  intact  animal  the  out- 
let of  the  thorax  be  restricted,  as  by  pressure  upon  the  trachea,  the  force  of  the 
inspiratory  movement  would  make  itself  felt  chiefly  upon  the  heart  and  the 
vessels,  and  it  is  under  such  circumstances  that  the  maximal  influences  of  in- 
spiration upon  the  circulation  are  observed.  The  lungs  on  the  one  hand  and 
the  heart  and  its  large  vessels  on  the  other  may  be  regarded  as  two  sacs  placed 
within  a  closed  expansible  cavity,  the  former  having  an  outlet  communicating 
with  the  external  air,  and  the  latter  having  inlets  and  outlets  communicating 
with  the  extrathoracic  blood-vessels,  both  being  dilated  when  the  thorax  ex- 
pands and  constricted  when  it  contracts.  Moreover,  the  blood-vessels  in  the 
lungs  may  be  compared  to  a  system  of  delicate  tubes  placed  within  a  closed 
distensible  bag  and  communicating  with  tubes  outside  of  the  bag,  simulating 
the  communication  of  the  venae  cavae  and  the  aorta  with  the  extrathoracic 
vessels.  When  such  a  bag  is  distended  the  tubes  undergo  elongation  and 
narrowing,  and  their  capacity  is  increased.  The  narrowed  vessels  also  tend 
to  be  expanded,  owing  to  the  negative  pressure  present  ;  and  thus  have  their 
capacity  further  increased.  The  lungs  in  the  same  way,  when  expanded  by 
the  act  of  inspiration,  exhibit  a  simultaneous  elongation  and  narrowing  of  the 
intrapulnionary  vessels,  which  results,  however,  in  an  increase  in  their  total 
capacity. 

I)urin<_r  expiration  negative  intrathoracic  pressure  becomes  less,  so  that 
there  is  a  gradual  return  of  the  elongated  and  narrowed  intrathoracic  vessels 
to  that  condition  which  existed  at  the  beginning  of  inspiration  ;  at  the  same 
time  the  intrapulnionary  vessels  are  not  only  subjected  to  the  passive  influ- 
ence of  the  declining  intrathoracic  pressure,  but  are  actively  squeezed,  as  it 
were,  between  the  air  in  the  lungs  on  one  side  and  the  expiratory  forces 
expelling  the  air  on  the  other.  Thus  we  have  during  expiration  passive  and 
active  agents  combining  to  bring  about  changes  in  the  capacity  of  the  intra- 
pulnionary vessels. 

The  mechanical  effects  of  the  movements  of  respiration  upon  blood-press- 


RESPIRATION. 


449 


lire  may  be  crudely  demonstrated  by  Hering's  device  (  Fig.  79).  The  chamber 
a  represents  the  thorax )  the  rubber  bottom  B  the  diaphragm  ;  c,  the  opening 
of  the  trachea;  e  d,  a  tube  leading  from  the  thoracic  cavity  to  the  manometer 
I,  by  means  of  which  intrathoracic  pressure  is  measured  ;  <;  is  a  vessel  contain- 
ing water,  colored  blue  in  imitation  of  venous  blood,  communicating  bv  means 
of  a  tube  with  an  oblong  flaccid  bag  F,  in  imitation  of  the  heart  and  the  intra- 
thoracic vessels,  and  finally  with  the  vessel  h  ;  v'  and  v  are  valves  in  imitation 
of  valves  in  the  heart  and  pulmonary  vein  and  aorta.  If  now  the  knob  K 
which  is  fastened  to  the  centre  of  the  diaphragm  be  pulled  down,  rarefaction 
of  the  air  within  the  chamber  occurs,  so  that  the  greater  external  pressure 
forces  air  through  the  tube  c  into  the  two  rubber  bags  (lungs) ;  at  the  same 
time  and  for  the  same  reason  water  is  forced  from  the  vessel  g  into  f,  which  is 
distended.  The  diaphragm  upon  being  released  is  drawn  up  in  part  by  virtue 
of  its  own  elasticity  and  in  part  by  the  negative  pressure  within  the  chamber. 
The  rubber  bags  are  emptied  by  their  own  natural  elastic  reaction.     At  the 


Fig.  79.— Hering's  device  to  illustrate  the  Influence  of  respiratory  movements  upon  the  circulation. 


same  time  the  distended   bag  F  contracts  on   its  contained  fluid,  forcing  it    into 

the  vessel  n,  the  valve  v  preventing  a  back-flow  into  G.     The  degri I"  force 

exerted  by  the  traction  on   the  diaphragm    is   read  from  the  scale  <m  the  man- 
ometer. 

This  simple  contrivance  teaches  us  that   during  the  entire  phase  of  inspira- 
tion there  is  a  condition  of  progressively  increasing  negative  pressure  within 
the  thorax,  and  that  not  only  is  air  aspirated   into  the  lungs,  but    that   blood  is 
Vol.  I.— 29 


450  ^.V   AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

drawn  into  the  large,  flaccid  vena?  cava?;  and  that  during  expiration  there  is  a 
gradual  diminution  of  negative  pressure  during  which  air  is  expelled  from  the 
lungs  and  blood  from  the  expanded  venae  cava?. 

The  increased  flow  into  the  thoracic  cavity  during  inspiration  is  favored  in 
it-  progress  through  the  pulmonary  vessels  by  the  increased  capacity  <»f  the 
lung-capillaries  and  by  the  fact  that  the  increased  negative  pressure  affects  the 
thin-walled  and  slightly  distended  pulmonary  veins  more  than  the  thick-walled 
and  more  distended  pulmonary  arteries,  so  that  the  "driving  force"  of  the  lung 
circulation,  which  is  essentially  the  difference  in  pressure  between  the  blood  in 
the  pulmonary  arteries  and  that  in  the  vein-,  is  thereby  increased  during  inspi- 
ration and  the  blood-current  is  driven  with  greater  velocity.  More  blood  thus 
being  brought  into  the  chest,  and  consequently  to  the  heart,  during  inspiration, 
and  less  resistance  being  offered  to  the  flow  of  the  blood  through  the  lungs, 
more  blood  must  ultimately  find  its  way  to  the  left  side  of  the  heart,  and  con- 
sequently into  the  general  circulation.  Li',  therefore,  the  general  capillary 
resistance  in  the  systemic  circulation  remains  the  same,  it  is  evident  that  an 
increased  blood-supply  to  the  left  ventricle  must  cause  the  general  blood-pres- 
sure to  rise.  That  this  rise  does  not  become  manifest  immediately  at  the 
beginning  of  inspiration  is  doubtless  owing  to  the  filling  of  the  flaccid  and 
partially  collapsed  large  veins  and  to  the  increased  capacity  of  the  intrapul- 
monary  vessels.  The  continuance  of  the  rise  for  a  short  time  after  the  ces- 
sation of  inspiration  is  due  apparently  to  the  partial  emptying  of  the  luug- 
vessels,  whereby,  owing  to  the  arrangement  of  the  heart- valves,  the  excess  of 
blood  is  forced   toward  the  left  side  of  the  heart. 

Besides  the  above  factors,  the  flow  of  blood  to  the  right  side  of  the  heart  is 
favored  by  the  pressure  transmitted  from  the  conjoint  actions  of  the  diaphragm 
and  the  abdominal  walls  through  the  abdominal  viscera  to  the  abdominal 
vessels.  The  pressure  upon  the  arteries  tends  to  drive  the  blood  toward  the 
lower  extremities  and  to  hinder  the  flow  from  the  heart;  in  the  veins, however, 
the  flow  toward  the  heart  is  encouraged,  while  that  from  the  extremities  is 
hindered.  The  rigid  walls  of  the  arteries  protect  them  from  being  materially 
affected,  but  the  flaccid  vein-  are  influenced  to  a  marked  degree;  while,  there- 
fore, the  How  from  the  left  side  of  the  heart  is  not  materially  interfered  with, 
that  through  the  veins  toward  the  right  side  is  appreciably  facilitated,  and  thus 
the  supply  of  blood  to  the  heart  is  increased.  The  effects  of  these  movements 
may  be  seen  after  section  of  the  phrenic  nerves,  which  causes  paralysis  of  the 
diaphragm,  when  it  will  be  noted  that  the  blood-pressure  curves  are  much  re- 
duced. This  diminution  is  attributed  to  two  causes — the  enfeebled  respiratory 
movements,  which  are  now  confined  to  the  ribs  and  the  sternum,  and  the 
absence  of  the  pressure  transmitted  from  the  diaphragm  through  the  abdominal 
organs  to  the  vein-.  If  in  such  an  animal  the  abdomen  be  periodically  com- 
pressed, in  imitation  of  the  effects  produced  by  the  contraction  of  the  dia- 
phragm, the  respiratory  curve-  may  be  restored  to  their  normal  height, 

During  expiration,  since  the  conditions  are  reversed  the  effects  also  must  be 
reversed.     The  increased  negative  intrathoracic  pressure  occasioned  by  inspira- 


RESPIRA  TIOX.  451 

tion  now  gives  place  to  a  gradual  diminution,  and  with  this  a  lessening  of  the 
aspiratory  action  due  to  the  sub-atmospheric  intrathoracic  pressure;  the  blood- 
supply  is  further  reduced  because  of  the  lessened  amount  of  blood  coming 
through  the  inferior  vena  cava;  the  abdominal  veins,  instead  of  being  com- 
pressed and  their  contents  forced  chiefly  toward  the  heart,  are  now  being 
filled;  finally,  during  the  shrinkage  of  the  lungs  the  intrapulmonary  vessels 
become  lessened  in  capacity,  and  thus  temporarily  force  more  blood  into  the 
left  side  of  the  heart  and  cause  the  brief  rise  of  arterial  pressure  observed  at 
the  beginning  of  expiration. 

Another  factor  believed  by  some  to  be  involved  in  the  respiratory  undula- 
tions in  blood-pressure  is  a  rhythmical  excitation  of  the  vaso-constrictor  centre 
in  the  medulla  oblongata,  asserted  to  occur  coincidently  with  the  inspiratory 
discharge  from  the  respiratory  centre.  This  has,  however,  been  disproved. 
Others  have  held  that  the  blood-pressure  changes  are  due  to  the  pressure  ex- 
erted by  the  expanding  lungs  upon  the  heart;  while  others  contend  that 
rhythmical  alterations  in  the  heart-beats  are  important.  This  latter  factor  is 
of  importance  in  man  and  in  the  dog,  in  which  there  is  a  distinct  increase  in 
the  rate  of  the  heart-beat  during  inspiration,  and  co-operates  in  producing  the 
general  rise  of  pressure  during  inspiration. 

The  Effects  on  the  Pulse. — During  inspiration  the  pulse-rate  is  more 
rapid  than  during  expiration.  If  we  cut  the  pneumogastric  nerves,  it  will  be 
seen  that,  while  the  rate  is  increased  as  the  result  of  the  section,  the  difference 
during  inspiration  and  expiration  is  abolished  ;  on  the  other  hand,  if  the  thorax 
be  widely  opened,  but  the  pneumogastric  nerves  are  left  intact,  the  inspiratory 
increase  in  the  rate  still  occurs.  This  indicates  that  the  cardio-inhibitory 
centre  is  either  less  active  during  inspiration  or  more  active  during  expiration, 
and  that  there  is  an  associated  activity  of  the  respiratory  and  cardio-inhibitory 
centres.  Why  this  sympathy  should  exist  between  the  respiratory  and  cardio- 
inhibitory  centres  we  do  not  know,  but  it  has  been  suggested  that  during  expi- 
ration the  blood  reaching  the  centres  is  less  highly  arterialized  than  during 
the  inspiratory  phase,  and  that  the  cardiac  centre  is  so  sensitive  to  the  difference 
as  to  be  affected,  and  thus  its  activity  is  somewhat  increased  during  the  expira- 
tory phase,  with  the  consequent  decrease  in  the  pulse-rate. 

During  inspiration  the  pulse-rate  is  not  only  higher  than  during  expiration, 
but  the  form  of  the  pulse-wave  is  affected.  The  systolic,  dicrotic,  and  >ir- 
ondary  waves  are  smaller  and  the  dicrotic  notch  is  more  pronounced,  SO  that 
the  dicrotic  character  of  the  curves  is  better  marked. 

The  Effects  of  Obstruction  of  the  Air-passages  and  of  the  Respira- 
tion of  Rarefied  and  Compressed  Air  on  the  Circulation. — The  blood- 
pressure  undulations  produced  during  quiet  breathing  become  marked  in  pro- 
portion to  the  depth  of  the  respiratory  movements.  Inspiration  or  expiration 
against  extraordinary  resistance — as  after  closing  the  mouth  and  nostrils,  or 
respiring  rarefied  or  compressed  air — may  materially  modify  the  circulatory  phe- 
nomena. When  we  make  the  most  forcible  inspiratory  effort,  the  air  passages 
being  fully  open,  not   only  is  there  a   full   expansion   of  the   lungs,  but    great 


452  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

diastolic  distention  of  the  heart  and  dilatation  of  the  intrathoracic  vessels ;  yet, 
notwithstanding  that  this  powerful  aspiratory  action  encourages  the  flow  of  an 
extraordinarily  large  amount  of  blood  into  the  thoracic-  vessels,  the  heart-beats 
may  be  very  small,  because  intrathoracic  negative  pressure  is  so  great  that  the 
thin-walled  auricles  meet  with  great  resistance  while  contracting;  in  conse- 
quence,  then,  of  this  forced  inspiratory  effort  little  blood  is  driven  through  the 
lungs  to  the  left  auricle  and  by  the  left  ventricle  into  the  general  circulation, 
ff  we  make  the  greatest  possible  expiratory  effort,  and  maintain  the  expira- 
tory phase  with  air-passages  open,  the  heart-beats  arc  small,  owing  to  the 
small  amount  of  blood  which  How-  through  the  venae  cavse  to  the  right  auri- 
cle, and  to  the  resistance  offered  by  the  compressed  intrapulmonary  vessels. 

If,  after  a  most  powerful  expiration,  we  close  the  mouth  and  nostrils  and 
make  a  powerful  inspiratory  effort,  the  aspiratory  effect  of  inspiration  on  the 
heart  and  the  blood-vessels  is  manifest  to  its  utmost  degree:  the  heart  and  the 
vessels  tend  to  undergo  great  dilatation,  the  blood-flow  to  the  right  auricle  and 
ventricle  is  increased,  the  intrapulmonary  vessels  and  the  heart  become  en- 
gorged, and,  owing  to  the  powerful  traction  of  the  negative  pressure  upon  the 
heart,  especially  upon  the  right  auricle,  very  little  blood  is  forced  through  the 
lungs  to  the  left  auricle  and  ventricle  and  subsequently  into  the  general  circu- 
lation, thus  causing  a  fall  of  blood-pressure;  indeed,  the  heart-sounds  and  the 
pulse  may  disappear.  If  now  we  make  the  most  forcible  inspiratory  effort, 
close  the  glottis,  and  make  a  powerful  expiratory  effort,  not  only  is  the  air  in 
the  lungs  subjected  to  high  positive  pressure,  but  the  heart  and  the  great 
vessels  partake  in  the  pressure-effects,  the  blood  being  forced  from  the  pul- 
monic circulation  into  the  left  auricle,  thence  by  the  ventricle  into  the  aorta, 
with  the  result  of  a  temporary  rise  of  blood-pressure.  The  pressure  upon  the 
intrathoracic  veins  is  so  great  that  the  flow  of  blood  into  the  chest  is  almost 
shut  off,  hence  the  veins  outside  the  thorax  become  very  much  distended,  as 
seen  in  the  superficial  veins  of  the  neck,  and  the  heart  is  pressed  upon  to  such 
an  extent  that,  together  with  the  lessened  supply  of  blood,  the  heart-sounds 
and  the  radial  pulse  may  disappear  and  the  blood-pressure  falls. 

The  respiration  into  or  from  a  spirometer  (p.  427)  containing  rarefied  or 
compressed  air  modifies  the  blood-pressure  curves.  Inspiration  of  rarefied  air 
causes  a  greater  rise  of  blood-pressure  than  when  respiration  occurs  at  normal 
pressure,  while  during  expiration,  although  the  blood-pressure  falls,  it  may 
remain  somewhat  above  the  normal.  The  increase  of  pressure  is  due  to  the 
aspiratory  effort  required  to  draw  the  air  into  the  lungs,  which  effort  also  makes 
itself  felt  to  a  more  marked  degree  upon  the  heart  and  the  intrathoracic  and 
intrapulmonary  vessels,  thus  increasing  the  blood-flow  through  the  pulmonary 
circulation.  During  expiration  air  is  aspirated  from  the  lungs  into  the  spi- 
rometer,  tending  to  dilate  the  intrathoracic  and  intrapulmonary  vessels  and  the 
heart  and  thus  to  aid  the  pulmonary  circulation.  After  a  time,  however,  there 
is  a  fall  of  blood-pressure  on  account  both  of  the  engorgement  of  the  thoracic 
vessels  and  the  accompanying  depletion  of  the  general  circulation,  and  of  the 
distention  of  the  heart  and  interference  with  its  contractions. 

In.-piration   of  compressed  air  lessens  the  extent  of,  and  may  prevent,  the 


RESPIRATION.  453 

inspiratory  rise,  or  it  may  cause  a  fall.  If,  upon  the  respiration  of  compressed 
air,  the  pressure  of  the  air  be  above  that  exerted  by  the  elastic  tension  of  the 
lungs,  no  effort  of  the  inspiratory  muscles  is  required,  the  chest  being  expanded 
by  the  pressure  of  the  air.  Therefore,  instead  of  an  increase  of  negative  intra- 
thoracic pressure,  as  in  normal  inspiration,  there  is  a  decrease,  and  negative 
intrathoracic  pressure  is  replaced  by  positive  pressure.  As  a  result,  the  blood- 
vessels and  the  heart,  instead  of  being  dilated  by  an  aspiratory  action,  are 
pressed  upon,  forcing  the  blood  into  the  general  circulation,  and  thus  causing  a 
transient  rise  of  pressure,  which  is,  however,  succeeded  by  a  fall  due  to  obstruc- 
tion to  the  flow  of  blood  through  the  heart  and  the  pulmonary  vessels.  Ex- 
piration into  compressed  air  causes  at  first  a  transient  increase  of  blood-pressure 
followed  by  a  fall,  the  former  being  due  to  the  forcing  of  some  of  the  blood 
from  the  intrathoracic  and  intrapulmonary  vessels  into  the  general  circulation, 
and  the  latter  to  obstruction  to  the  blood-flow  through  the  heart  and  the  pul- 
monary circulation. 

When  individuals  are  exposed  to  compressed-  air,  as  in  a  pneumatic  cabinet, 
or  to  rarefied  air,  as  in  ballooning,  the  effects  on  the  circulation  become  of  a 
very  complex  character,  owing  chiefly  to  the  additional  influences  of  the 
abnormal  pressure  upon  the  peripheral  circulation ;  moreover,  the  effects  of 
breathing  against  obstructions  or  of  respiring  rarefied  or  compressed  air  may 
be  materially  influenced  by  secondary  effects  resulting  from  excitation  of  the 
cardiac  and  vaso-motor  mechanisms. 

In  artificial  respiration,  as  ordinarily  performed  in  the  laboratory,  air  is 
periodically  forced  into  the  lungs  by  a  pair  of  bellows  or  a  pump,  and  is  ex- 
pelled from  the  lungs  by  the  normal  elastic  and  mechanical  factors  of  expira- 
tion. When  the  lungs  are  inflated  the  pulmonary  capillaries  are  subjected  to 
opposing  forces — the  positive  pressure  of  the  air  within  the  lungs  on  one  hand, 
and  the  resistance  of  the  thoracic -walls  on  the  other — so  that  the  blood  is 
squeezed  out,  thus  momentarily  increasing  the  blood-pressure,  but  subsequently 
retarding  the  current  and  consequently  lowering  the  pressure.  During  expira- 
tion the  pressure  is  removed  and  the  blood-flow  is  encouraged  :  there  is,  there- 
fore, a  temporary  fall  during  the  filling  of  the  pulmonary  vessels,  followed  by 
a  rise  due  to  the  removal  of  the  obstruction.  If  the  air  is  aspirated  from  the 
lungs,  the  rise  of  the  pressure  is  augmented,  owing  to  the  further  dilatation  of 
the  intrapulmonary  capillaries ;  hence,  in  artificial  respiration,  during  the  in- 
spiratory phase  the  blood-pressure  curves  arc  reversed,  there  being  a  primary 
transient  rise  followed  by  a  fall,  and  during  the  expiratory  phase  a  transienl 
fall  followed  by  a  rise.  In  normal  respiration  the  oscillations  are  due  essen- 
tially to  the  changes  in  capacity  of  the  intrapulmonary  vessels  caused  essen- 
tially by  the  alterations  in  their  length,  while  in  artificial  respiration  the 
effects  of  these  alterations  are  opposed  and  superseded  by  those  due  directly 
to  positive  intrapulmonary  pressure. 

J.  Special  Respiratory  Movements. 
The  rhythmical  expansion-  and  contractions  of  the  thorax  which  we  under- 
stand as  respiratory  movements  have  for  their  object   the  ventilation  of  the 


\'<\  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

] u iiLf-.  There  are,  however,  other  movements  which  possess  certain  respiratory 
characters,  but  which  are  for  entirely  different  purposes,  hence  they  are  spoken 
of  as  special  or  modified  respiratory  movements.  Some  of  these  movements 
are  purposeful  in  character,  others  are  spasmodic;  some  are  voluntary  or  in- 
voluntary, "i-  pi  )>>(■-»>  liiith  volitional  ami  in  volitional  characteristics;  some  are 
peculiar  to  certain  species,  etc.  Among  such  movements  are  coughing,  hawking, 
sneezing,  laughing,  crying,  sobbing,  sighing,  yawning,  snoring,  gargling,  hic- 
cough, neighing,  braying,  growling,  etc. 

In  coughing  a  preliminary  inspiration  is  followed  by  an  expiration  which  is 
frequently  interrupted,  the  glottis  being  partially  closed  at  the  time  of  the 
occurrence  of  each  interruption,  so  that  a  series  of  characteristic  sounds  is 
caused.  The  air  is  forcibly  ejected  through  the  mouth,  and  thus  foreign  parti- 
cles, such  as  mucus  in  the  respiratory  passages,  may  be  expelled.  Coughing 
may  be  either  voluntary  or  reflex. 

Hawking  is  somewhat  similar  to  coughing.  The  glottis  is,  however,  open 
during  the  expiratory  act,  and  the  expiration  is  continuous.  The  current  of 
air  is  forced  through  the  contracted  passage  between  the  root  of  the  tongue 
and  the  soft  palate.     Hawking  is  a  voluntary  act. 

In  sneezing  a  deep  inspiration  is  followed  by  a  forcible  expiratory  blast 
directed  through  the  uose;  the  glottis  is  open,  and  should  the  oral  passage  be 
open,  which  is  not  usually  the  case,  a  portion  of  the  blast  is  forced  through  the 
mouth.  Sneezing  is  usually  a  reflex  act  commonly  excited  by  irritation  of  the 
fibres  of  the  nasal  branches  of  the  fifth  pair  of  cranial  nerves.  Peculiar  sen- 
sations in  the  nose  give  us  a  premonition  of  sneezing;  at  such  a  time  the  act 
may  be  prevented  by  firmly  pressing  the  finger  upon  the  upper  lip. 

In  laughing  there  is  an  inspiration  followed,  as  in  coughing,  by  a  repeatedly- 
interrupted  expiration  during  which  the  glottis  is  open  and  the  vocal  cords  are 
thrown  into  vibration  with  each  expiratory  movement.  The  expirations  are 
not  as  forcible  as  in  coughing,  the  mouth  is  wide  open,  and  the  face  has  a 
characteristic  expression  due  to  the  contraction  of  the  muscles  of  expression. 

Crying  bears  a  close  relationship  to  laughing — so  much  so  that  at  times  it 
is  impossible  to  distinguish  between  the  two;  hence  one  may  readily  pass  into 
the  other,  as  frequently  occurs  in  cases  of  hysteria  and  in  young  children. 
The  chief  differences  between  the  two  are  in  the  rhythm  and  the  facial  expres- 
sion. A  secretion  of  tears  is  an  accompaniment  of  crying,  but  not  so  of 
laughing,  except  during  very  hearty  laughter.  Crying  normally  is  involun- 
tary ;  laughing  may   be  either   voluntary  or  involuntary. 

Sobbing,  which  is  apt  to  follow  a  long  period  of  crying,  is  characterized  as 
being  a  series  of  spasmodic  inspirations  during  each  of  which  the  glottis  is 
partially  closed,  and  the  series  is  loll,, wed  by  a  long, quiet  expiration.  This  is 
usually  involuntary,  but  may  sometimes  be  arrested  volitionally.  In  sighing 
there  is  a  long  inspiration  attended  by  a  peculiar  plaintive  sound.  The  mouth 
may  be  either  closed  or  partially  open.      Sighing  i-  usually  voluntary. 

Yawning  has  certain  feature-  like  the  preceding.  There  occurs  a  long, 
deep  inspiration  during  which  the  mouth  is  stretched  wide  open,  and  there  is 
usually  a  simultaneous  strong  contraction   of  certain  of  the  muscles  of  the 


BESPIRA  TION.  455 

shoulders  and  the  back  ;  the  glottis  is  wide  open,  and  inspiration  is  accompa- 
nied by  a  peculiar  sound  ;  expiration  is  short.  Yawning  may  be  either  volun- 
tary or  involuntary. 

In  snoring  the  mouth  is  open,  and  the  inflow  and  outflow  of  air  throws  the 
uvula  and  the  soft  palate  into  vibration.  The  sound  produced  is  more  marked 
during  inspiration,  and  may  even  be  absent  during  expiration.  It  is  more  apt 
to  occur  when  the  individual  is  lying  on  his  back  than  when  in  any  other 
posture.     Snoring  is  usually  involuntary,  but  it  may  be  volitional. 

In  gargling  the  fluid  is  held  between  the  tongue  and  the  soft  palate  and  air 
is  expired  through  it  in  the  form  of  bubbles. 

In  hiccough  there  is  a  sudden  inspiratory  effort  caused  by  a  spasmodic 
twitch  of  the  diaphragm  and  attended  by  a  sudden  closure  of  the  glottis,  so 
that  the  inspiratory  movement  is  suddenly  arrested,  thus  causing  a  characteris- 
tic sound.  Hiccough  is  sometimes  not  only  distressing,  but  may  be  even  seri- 
ous or  fatal  in  its  consequences.  It  is  especially  apt  to  occur  in  cases  of  gastric 
irritation,  in  certain  forms  of  hysteria,  in  alcoholism,  in  uraemia,  etc. 

Besides  the  above  special  respiratory  movements,  others  are  observed  in 
certain  species  of  animals,  such  as  whining,  neighing,  braying,  roaring,  bellow- 
ing, bawling,  barking,  purring,  growling,  etc. 

Of  all  these  modified  respiratory  movements,  coughing  possesses  to  the 
clinician  the  most  interest,  because  it  not  only  may  express  an  abnormal  condi- 
tion of  some  portion  of  the  lungs,  trachea,  or  larynx,  but  may  indicate  irrita- 
tion in  even  remote  and  entirely  unassociated  parts.  Thus,  coughing  may  be 
the  result  of  irritation  in  the  nose,  ear,  pharynx,  stomach,  liver,  spleen,  intes- 
tines, ovaries,  testicle,  uterus,  or  mamma.  Coughs  which  are  not  dependent 
upon  irritation  of  the  larynx,  trachea,  or  luugs  are  distinguished  as  sympa- 
thetic or  reflex  coughs.  The  term  "reflex"  is  a  bad  one,  however,  inasmuch 
as  all  coughs  are  essentially  or  solely  reflex. 

K.  The  Nervous  Mechanism  of  the  Respiratory  Movements. 

The  movements  of  respiration  are  carried  on  involuntarily  and  automati- 
cally— that  is,  they  recur  by  virtue  of  the  activity  of  a  self-governing  mech- 
anism. Each  respiratory  act  necessitates  a  finely  co-ordinated  adjustment  of 
the  contractions  of  a  number  of  muscles,  which  adjustment  is  dependent  upon 
the  operations  of  a  dominating  or  controlling  nerve-centre  located  in  the 
medulla  oblongata,  and  known  as  the  respiratory  centre.  Besides  this  centre, 
others  of  minor  importance  have  been  asserted  to  exist  in  certain  parts  of  the 
cerebro-spinal  axis;  these  centres  are  distinguished  as  subsidiary  or  subordinate 
respiratory  centres.  Connected  with  the  respiratory  centre  are  afferent  and 
efferent  respiratory  nerves. 

The  Respiratory  Centres. — After  removal  of  all  parts  of  the  brain  except 
the  spinal  bulb,  rhythmical  respiratory  movements  may  still  continue,  but  aftei 
destruction  of  the  lower  part  of  the  bulb  they  at  once  cease.  These  facts  indi- 
cate that  the  centre  for  these  movements  is  in  the  medulla  oblongata,  and  this 
conclusion  is  substantiated  by  the  results  of  other  experiments  upon  this 
region.     According  to  the  observations  of  Flourcns,  the  respiratory  centre  is 


456  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

located  in  an  area  about  •">  millimeters  wide  between  the  nuclei  of  the  pneumo- 
gastric  and  spinal  accessory  nerves  in  the  lower  end  of  the  calamus  scriptorius. 
When  this  region  was  destroyed  he  found  that  respiratory  movements  ceased 
and  death  ensued,  consequently  he  tinned  it  the  noeud  vital,  or  vital  knot. 
The  results  of  various  investigations  show,  however,  that  Flourens'  area,  as 
well  as  certain  other  parts  of  the  medulla  oblongata  that  have  been  looked 
upon  by  others  as  being  respiratory  centres,  are  not  such,  but  are  largely  or 
wholly  collections  of  nerve-fibres  which  arise  chiefly  in  the  roots  of  the  vagal, 
spinal  accessory,  glosso-pharyngeal,  and  trigeminal  nerves,  and  which  there- 
fore are  probably  nerve-paths  to  and  from  the  respiratory  centre.  Moreover, 
excitation  of  the  rweud  vital  does  not  excite  respiratory  movements,  but  simply 
increases  the  tonicity  of  the  diaphragm  ;  nor  is  the  destruction  of  the  area 
always  followed  by  a  cessation  of  respiration.  While  the  precise  location  of 
the  centre  is  still  in  doubt,  there  is  abundant  evidence  to  justify  the  belief  in 
its  existence  in  the  lower  portion  of  the  spinal  bulb. 

The  centre  is  bilateral,  one  half  being  situated  on  each  side  of  the  median 
line,  the  two  parts  being  intimately  connected  by  commissural  fibres,  thus  con- 
stituting physiologically  a  single  centre.  This  union  may  be  destroyed  by 
section  along  the  median  line.  Each  half  acts  more  or  less  independently  of, 
although  synchronously  with,  the  other,  and  each  is  connected  with  the  lungs 
and  the  muscles  of  respiration  of  the  corresponding  side.  These  facts  are 
rendered  manifest  in  the  following  observations:  If  a  section  be  made  in  the 
median  line  so  as  to  cut  the  commissural  fibres,  the  respiratory  movements  on 
the  two  sides  continue  synchronously  ;  if  now  the  portion  of  the  centre  on  the 
one  side  be  destroyed,  the  respiratory  movements  on  the  corresponding  side  tem- 
porarily or  permanently  cease.  If  after  section  in  the  median  line  one  pneumo- 
gastric  nerve  be  divided,  the  sensory  impulses  conveyed  from  the  lungs  on  the 
side  of  section  to  the  corresponding  half  of  the  respiratory  centre  are  prevented 
from  reaching  the  centre,  causing  the  movements  of  the  respiratory  muscles  on 
the  same  side  to  be  slower  and  the  inspirations  stronger  as  compared  with  those 
on  the  opposite  side  ;  if  both  pneumogastrics  be  divided,  and  the  central  end  of 
one  of  the  cut  nerves  be  excited  high  in  the  neck  by  a  strong  current,  the  respi- 
ratory movements  on  the  same  side  may  be  arrested,  yet  they  may  continue  on 
the  opposite  side.  These  facts  indicate  that  each  half  is  in  a  measure  inde- 
pendent of  the  other.  The  operations  in  the  two  parts  are,  however,  inti- 
mately related,  a-  shown  by  the  fact  that  if  the  commissural  fibres  between 
the  halves  are  intact,  excitation  or  depression  of  one  half  is  to  a  certain  degree 
shared  by  the  other.  Thus,  after  section  of  one  vagus  not  only  are  the  respi- 
ratory  movements  less  frequeni  and  the  inspirations  stronger  on  the  side  of 
the  section,  but  there  i-  a  corresponding  condition  on  the  opposite  side;  simi- 
larly, excitation  of  the  central  end  of  the  cul  nerve  increases  the  respiratory 
rate  both  on  the  same  and  on  the  opposite  side.  Consequently,  while  there  is 
more  or  less  independence  of  the  halves,  the  two  are  physiologically  so 
intimately  associated  as  to  constitute  a  common  or  single  centre. 

Moreover,  each  of  the  halve-  may  be  supposed  to  consist  of  two  distinct 
portions,  one  of  which,  upon  excitation,  gives  rise  to  contraction  of  inspiratory 


RESPIBA  TION.  457 

muscles,  the  other  to  contraction  of  expiratory  muscles;  hence  they  are  spoken 
of  as  inspiratory  and  expiratory  parts  of  the  respiratory  centre,  or  as  inspi- 
ratory and  expiratory  centres.  Moderate  excitation  of  the  inspiratory  centre 
causes  not  only  contraction  of  inspiratory  muscles,  hut  au  increase  in  the 
respiratory  rate;  and  if  the  irritation  be  sufficiently  strong,  there  occur-  a 
spasmodic  arrest  of  the  respiratory  movements  in  the  inspiratory  phase.  On 
the  contrary,  excitation  of  the  expiratory  centre  causes  contraction  of  expi- 
ratory muscles  and  diminishes  the  respiratory  rate;  powerful  excitation  of  the 
same  centre  is  followed  by  arrest  of  movements  in  the  expiratory  phase. 
The  inspiratory  portion  may  therefore  be  regarded  not  only  as  being  spe- 
cifically connected  with  inspiratory  muscles,  but  in  the  sense  of  an  accelerator 
centre;  and  the  expiratory  portion  maybe  regarded  as  being  similarly  con- 
nected with  expiratory  muscles,  and  as  being  an  inhibitor)/  centre.  When  the 
two  are  conjointly  excited  the  accelerator  effect  prevails,  because  under  ordinary 
circumstances  the  accelerator  element  of  the  centre  seems  more  excitable  and 
potent  than  the  inhibitory ;  therefore,  when  the  centre  as  a  whole  is  irritated, 
it  manifests  an  accelerator  character. 

In  addition  to  this  centre,  the  existence  of  subsidiary  centres  is  claimed, 
situated  both  in  the  brain  and  in  the  spinal  cord.  One  centre  has  been  located 
in  the  rabbit  in  the  tuber  cinereum,  which  has  been  named  a  polypnceic  centre, 
because  when  excited  the  respirations  are  rendered  extremely  frequent.  The 
sensitiveness  of  this  centre  is  readily  demonstrated  by  subjecting  an  animal 
to  a  high  external  temperature,  when  a  marked  increase  of  the  respiratory  rate 
follows;  if  now  the  tuber  cinereum  be  destroyed,  there  occurs  an  immediate 
cesssation  of  the  accelerated  movements.  Another  area  has  been  located  in 
the  optic  thalamus  in  the  floor  of  the  third  ventricle ;  this  centre  is  believed 
to  be  excited  by  impulses  carried  by  the  nerves  of  sight  and  hearing,  and 
when  irritated  causes  an  acceleration  of  the  respiratory  rate,  and  when  strongly 
excited  arrests  respiration  during  the  inspiratory  phase  ;  hence  it  is  regarded 
as  an  inspiratory  or  accelerator  centre.  Another  centre  has  been  Located  in 
the  anterior  pair  of  the  corpora  quadrigeniina  :  it  causes  expiratory  and  inhibi- 
tory effects,  and  may  therefore  be  placed  among  the  expiratory  or  inhibitory 
centres.  An  inspiratory  or  accelerator  centre  has  been  recorded  as  existing  in 
the  posterior  pair  of  the  corpora  quadrigemina  and  the  pons  Varolii.  The 
nuclei  of  the  triyemini  are  also  said  to  act  as  inspiratory  or  accelerator  centres. 
Respiratory  centres  are  likewise  claimed  to  exist  in  the  brain-cortex,  h  is 
very  doubtful,  however,  whether  or  not  these  so-called  subsidiary  respiratory 
centres  should  be  regarded  as  being  of  a  specific  character.  In  any  event,  we 
cannot  suppose  that  these  centres  are  capable  of  evoking  directly  respiratory 
movements,  [f  they  exist,  they  are  probably  connected  with  the  medullary 
centre,  through  which  (hey  exert  their  influence  on  the  respiratory  movements. 
The  existence  of  a  respiratory  centre  in  the  spinal  cord  is  also  doubtful. 
The  chief  reason  for  the  claim  of  its  existence  i<  that  respiratory  movements 
may  for  a  time  be  observed  after  section  of  the  cerebro-spinal  ;i\i-  at  the  junc- 
tion of  the  spinal  cord  and  bulb.  In  new-born  animal-  after  such  section 
respiratory  movements  may  continue  for  some  time,  strychnine  rendering  them 


458  AN    AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

more  pronounced.  Again,  animals  in  which  respiration  has  been  artificially 
maintained  for  a  long  time  may,  alter  section  of  the  cord  at  the  junction  with 
the  bulb,  exhibit  respiratory  movements  after  artificial  respiration  has  been 
suspended.  The  respiratory  movements  under  these  circumstances  are,  how- 
ever, of  a  spasmodic  character,  and  distinctly  unlike  the  co-ordinated  rhythmi- 
cal movements  observed  in  normal  animals;  the  movements  are  rather  of  the 
nature  of  spasms  simulating  normal  respirations. 

The  Rhythmic  Activity  of  tin  Respiratory  Centre. — The  rhythmic  sequence 
of  the  respiratory  movements  is  due  to  periodic  discharges  from  the  respiratory 
centre.  The  cause  of  this  periodicity  is  still  obscure,  but  the  fact  that  the 
rhythm  continues  after  the  combined  section  of  the  vagi  and  the  glosso-pharyn- 
geal  nerves,  of  the  spinal  cord  in  the  lower  cervical  region,  of  the  posterior 
roots  of  the  cervical  spinal  nerves,  and  of  the  spinal  bulb  from  the  parts 
above,  indicates  that  the  rhythm  is  inherent  in  the  nerve-cells,  and  is  not 
caused  by  external  stimuli  carried  to  the  centre  through  afferent  nerve-fibres. 
Loewy1  has  shown  that  under  the  above  circumstances,  when  the  centre  is  iso- 
lated from  afferent  nerve-impulses,  the  rhythmical  activity  of  the  centre  is  due  to 
the  blood,  which,  while  acting  as  a  continuous  excitant,  causes  discontinuous  or 
periodic  discharges,  so  that,  although  we  usually  speak  of  the  activity  of  the 
respiratory  centre  as  being  automatic — that  is,  not  immediately  dependent  upon 
external  stimuli — yet  as  a  matter  of  fact  the  apparently  automatic  discharges 
are  in  realitv  due  to  the  stimulation  by  the  blood;  the  centre  is  therefore  auto- 
matic only  with  reference  to  external  nerve-stimulation. 

The  rhythm  as  well  as  the  rate,  force,  and  other  characters  of  the  discharges 
may  be  affected  materially  by  the  will  and  emotions:  by  the  composition, 
Bupply,  and  temperature  of  the  blood;  and  especially  by  certain  afferent  im- 
pulses, pre-eminently  those  originating  in  the  pneumogastric  nerves.  As  to 
the  influence  of  the  will  and  emotions,  we  are  able,  as  is  well  known,  to  modify 
voluntarily  to  a  certain  extent  the  rhythm  and  other  characters  of  the  respira- 
tions, while  the  striking  effect  of  emotions  upon  respiratory  movements  is  a 
matter  of  almost  daily  observation.  The  importance  of  the  composition  of 
the  blood  is  manifested  by  the  marked  effect  upon  the  respirations  when  the 
blood  is  deficient  iii  ( ),  when  it  contains  an  excess  of  CO,,  and  during  muscu- 
lar activity,  when  in  the  blood  there  is  a  relative  abundance  of  certain  products 
resulting  from  muscular  metabolism.  If  the  blood-supply  to  the  centre  is 
diminished,  as  after  severe  hemorrhage  or  after  clamping  the  aorta  so  as  to 
interfere  with  the  cerebral  circulation,  the  respirations  are  less  frequent  and 
the  rhythm  is  affected,  the  form  of  breathing  having  a  Cheyne-Stokes  char- 
acter (p.  424) ;  conversely,  an  increase  in  the  blood-supply  causes  an  increase 
in  the  rate.  An  increase  or  decrease  in  the  temperature  of  the  blood  induces 
corresponding  changes  in  the  rate;  thus,  in  fever  the  frequency  of  the  move- 
ment- increases  almost  pari  passuvnth  the  augmentation  of  temperature,  while 
if  the  temperature  of  the  blood  be  reduced  by  applying  ice  to  the  carotids,  the 
rate  is  lessened. 

1  Pfluger'a  Archivf.  Physiologic.,  1889,  Bd.  xlii.  S.  245-281. 


RESPIRA  TION.  459 

Afferent  impulses  exercise  an  important,  and  practically  a  continuous,  influ- 
ence. After  section  of  one  pneumogastric  nerve  the  respirations  are  somewhat 
less  frequent;  after  section  of  both  nerves  the  respirations  become  considerably 
less  frequent  and  deeper  and  otherwise  changed.  If  we  stimulate  the  central 
end  of  one  of  these  cut  nerves  below  the  origin  of  the  laryngeal  branches  by 
a  current  of  electricity  of  moderate  intensity,  the  respiratory  rate  may  be  in- 
creased, and  we  may  be  able  to  restore,  or  even  exceed,  the  normal  frequency. 
The  fact  that  section  of  these  nerves  is  followed  by  a  diminution  of  the  rate 
and  that  excitation  of  the  central  end  of  the  cut  nerve  causes  an  increase  leads 
us  to  believe  that  the  pneumogastric  nerves  are  continually  conveying  impulses 
from  the  lungs  to  the  respiratory  centre,  which  impulses  in  some  way  increase 
the  number  of  discharges,  and  thus  the  respiratory  rate.  The  centre  may  be 
excited  or  depressed  by  excitation  of  the  cutaneous  nerves  and  the  sensory 
nerves  in  general ;  thus,  external  heat  accelerates,  while  a  dash  of  cold  water 
may  either  accelerate  or  inhibit,  respiratory  movements.  Excitation  of  the 
glosso-pharyngeal  nerves  inhibits  the  respirations.  Such  inhibition  occurs 
during  deglutition  to  avoid  the  risk  of  introducing  foreign  bodies  into  the 
larynx.  Similar  respiratory  inhibition  may  be  induced  by  excitation  of  the 
superior  laryngeal  nerves,  when,  if  the  degree  of  irritation  be  sufficiently 
strong,  complete  arrest  of  the  respiratory  movements  may  occur.  Strong  irri- 
tation of  the  olfactory  nerves  and  of  the  fibres  of  the  trigemini  distributed  to 
the  nasal  chambers  excites  expiration  and  may  be  followed  by  complete  inhibi- 
tion of  the  respiratory  movements;  strong  irritation  of  the  optic  and  auditory 
nerves  excites  inspiratory  activity ;  and  irritation  of  the  sciatic  nerve  causes  an 
increase  of  the  rate,  and  may  or  may  not  affect  the  depth  of  breathing. 

The  study  of  the  rhythmic  activity  of  the  respiratory  centre  is  further 
complicated  by  the  fact  that  there  is  not  only  a  rhythmic  sequence  of  the  res- 
pirations, but  a  rhythmic  alternation  of  inspiratory  and  expiratory  move- 
ments. While  it  is  true  that  in  ordinary  quiet  expiration  but  little  of  the 
muscular  element  is  present, yet  forced  expiration  is  a  well-defined  co-ordinated 
muscular  act.  The  mechanism  whereby  this  alternation  is  broughl  about  is 
not  understood.  Some  believe  that  the  pneumogastric  nerves  contain  both 
inspiratory  and  expiratory  fibres  which  are  connected  with  corresponding  pails 
of  the  respiratory  centre  and  alternately  convey  their  respective  impulses  to 
the  centre,  inspiratory  impulses  being  excited  during  expiration  and  expiratory 
impulses  during  inspiration  (p.  397).  These  impulses  are,  however,  not  indis- 
pensable to  the  alternation  of  inspiration  and  expiration,  because  these  acts 
follow  each  other  regularly,  even  after  the  isolation  of  the  respiratory  centre 
from  the  lungs  by  section  of  the  pneumogastric  nerves. 

Thus  we  may  conclude  that  the  rhythmical  discharges  from  the  centre  are 
due  primarily  to  an  inherent  properly  of  periodic  activity  of  the  nerve-cells 
constituting  the  respiratory  centre  and  maintained  by  the  blood,  and  that  the 
rhythm,  rate,  and  other  characters  of  these  discharges  may  be  affected  by  the 
will  and  the  emotions,  by  the  composition,  supply,  and  temperature  of  the 
blood,  and  by  various  afferent  impulses.     The  chief  factors  are,  under  ordi- 


460  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

nary  circumstances,  the  quantities  of  O  and  C02  in  the  blood,  and  the  impulses 
conveyed  from  the  lungs  by  the  fibres  of  the  pneumogastric  nerves. 

The  Afferent  Respiratory  Nerves. — The  chief  of  these  nerves  are  the 
pneumogastric,  glossopharyngeal,  trigeminal,  and  cutaneous  nerves.  The  im- 
portant part  taken  by  them  in  the  regulation  of  the  respiratory  movements  has 
frequently  been  alluded  to  in  connection  with  the  respiratory  centres.  Their 
functions,  however,  are  of  sufficient  importance  to  demand  special  and  detailed 
consideration. 

The  pneumogastric  nerves  are  pre-eminently  the  most  important.  Their 
functions  may  be  studied  by  comparing  the  phenomena  before  and  after  section 
of  one  or  of  both  nerves,  and  from  the  results  following  excitation  by  stimuli 
of  varying  quality  and  strength  under  normal  and  abnormal  conditions. 

Section  of  one  pneumogastric  may  be  without  effect  or  be  followed  by  a 
transitory,  slight  diminution  of  the  respiratory  rate;  by  slower  and  deeper 
movements;  by  stronger,  deeper,  and  longer  inspirations;  by  unaltered  or 
longer  or  shorter  expirations;  and  probably  by  active  expirations.  These 
effects  are  transient,  and  the  normal  respiratory  movements  are  usually  restored 
within  a  half  hour.  Section  of  both  nerves  is  sooner  or  later  followed  by  a 
diminution  of  the  respiratory  rate;  by  slow,  deep,  powerful  inspirations;  by 
active  expiration  ;  and  by  a  pause  between  expiration  and  inspiration.  The 
immediate  results  are  variable  unless  certain  precautions  are  taken  to  prevent 
irritation  of  the  central  ends  of  the  cut  nerves.  If  the  ends  are  allowed  to 
fall  back  into  the  wound,  the  respirations  may  become  irregular;  or  they  may 
be  less  frequent,  with  weakened  inspirations,  spasmodic  expirations,  and  pro- 
longed expiratory  pauses.  The  explanation  of  these  variable  results  is  found 
in  the  fad  that  the  expiratory  fibres  are  more  sensitive  to  very  weak  stimulus 
than  the  inspiratory  fibres,  and  that  the  mechanical  irritation  caused  by  the 
section,  and  the  excitation  due  to  the  electric  current  in  the  cut  ends  of  the 
nerves  that  is  established  when  the  central  end  of  the  nerve  is  replaced  in  the 
wound,  excite  expiratory  impulses  and  cause  expiratory  phenomena;  if  the 
irritation  be  stronger,  both  inspiratory  and  expiratory  impulses  are  excited, 
thus  causing  uncertain  results,  varying  as  one  or  the  other  is  the  stronger.  If 
irritation  be  prevented,  section  is  at  once  followed  by  typical  slow,  deep 
respirations. 

Stimulation  of  the  central  end  of  the  cut  vagus,  the  other  nerve  being 
intact,  is  followed  by  variable  results  dependent  upon  the  character  of  the 
stimulus.  Chemical  stimuli,  such  as  a  solution  of  sodium  carbonate,  excite 
the  expiratory  fibres;  mechanical  stimuli,  the  inspiratory  fibres;  electrical 
stimuli,  expiratory  or  inspiratory  fibres  or  both,  according  to  the  strength  of 
the  current.  Single  induction  shocks  are  without  effect,  but  a  tetanizing 
current  is  very  effective.  Should  that  current  which  will  elicit  the  least 
response  be  used,  the  breathing  is  rendered  less  frequent,  the  inspirations  are 
weakened,  and  the  expirations  may  be  active  and  lengthened;  in  other  words, 
there  are  present  the  same  phenomena  which  often  immediately  follow  section 
of  both  nerve-  when  the  cul  end-  are  allowed  to  fall  back  into  the  wound  and 


RESPIRA  TION.  461 

thus  establish  an  exciting  electric  current  which  affects  expiratory  fibres.  If 
the  strength  of  the  current  be  increased,  these  effects  give  place  to  those  of  an 
opposite  character,  the  respirations  becoming  more  frequent  and  the  inspi- 
rations more  marked  in  depth  and  force,  the  explanation  of  this  difference 
being  that  the  stronger  current  has  also  excited  inspiratory  fibres,  so  that  now 
both  expiratory  and  inspiratory  impulses  are  generated,  but  the  latter,  being 
more  potent  in  their  influences,  cause  acceleration  of  the  rate  and  accentuated 
inspirations.  The  effects  following  stimulation  of  the  central  end  of  the  cut 
vagus  by  a  current  of  moderate  strength  are  best  observed  after  both  nerves  have 
been  divided  and  when  there  exist  slow,  deep,  powerful  respirations.  Under 
such  circumstances  stimulation  of  the  central  end  of  one  of  the  vagi  is  followed 
at  once  by  an  increase  in  the  respiratory  rate  and  a  return  of  the  general  char- 
acters of  the  inspiratory  and  expiratory  phases  toward  the  normal ;  and  if  the 
degree  of  excitation  be  properly  adjusted,  the  normal  rate  and  normal  charac- 
ter of  breathing  may  be  restored.  Still  stronger  excitation  further  accelerates 
the  rate,  causing  the  respiratory  acts  to  follow  each  other  with  such  frequency 
that  inspiration  begins  before  the  expiratory  act  (relaxation  of  the  inspiratory 
muscles)  has  been  completed.  The  inspiratory  muscles  are  therefore  never 
completely  relaxed.  With  a  further  increase  of  stimulus  the  expiratory 
relaxation  becomes  less  and  less,  until  finally  the  respirations  are  brought  to  a 
standstill  in  the  inspiratory  phase,  the  inspiratory  muscles  being  in  tetanus. 

If  the  nerves  be  fatigued  from  over-excitation  or  if  the  animal  be 
thoroughly  chloralized,  stimulation  of  the  central  end  of  the  cut  nerve  by  a 
strong  current  is  no  longer  followed  by  inspiratory  stimulation,  but  is  followed 
by  expiratory  stimulation  (the  inspirations  being  shortened  and  weakened,  the 
expirations  prolonged  and  spasmodic)  and  by  long  pauses  between  expiration 
and  inspiration.  If  the  excitation  be  sufficiently  strong,  arrest  of  respiration 
occurs  in  the  expiratory  phase. 

It  will  be  observed  from  the  above  results  that  electrical  irritation  of  the 
central  end  of  the  cut  pneumogastric  may  be  followed  by  effects  of  an  oppo- 
site character,  extremely  weak  irritation  causing  expiratory  stimulation  (weaker 
and  shorter  inspirations,  prolonged  and  active  expirations,  expiratory  pan--. 
and  diminished  respiratory  rate) ;  whereas  moderate  irritation  causes  inspiratory 
stimulation  (stronger  and  deeper  inspirations  and  increased  respiratory  rate). 
These  diverse  results  are  explained  by  the  fact  that  these  nerves  contain  two 
kinds  of  fibres  having  opposite  functions:  fibres  of  one  kind  convey  impulses 
which  affect  the  expiratory  centre ;  those  of  the  other  kind  convey  impulses 
which  affect  the  inspiratory  centre.  The  former  are  more  susceptible  to  weak 
electrical  stimulation,  and  thus  their  presence  may  be  elicited  by  the  weakest 
stimulus  capable  of  causing  any  response.  At  the  same  time  they  arc  less 
readily  exhausted,  so  that  if  the  vagi  be  subjected  to  prolonged  stimulation 
by  a  strong  current,  the  inspiratory  fibres  are  exhausted  before  the  expiratory 
fibres.  For  moderate  and  strong  currents  the  inspiratory  fibres  are  affected 
to  a  greater  degree  than  the  expiratory  fibres,  therefore  inspiratory  stimula- 
tion predominates. 


462  AN    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

Both  Bets  of  fibres  convey  impulses  which  have  their  origin  essentially  in 
the  peripheries  of  the  pneumogastric  nerves  in  the  lungs;  but  expiratory 
impulses  may  arise  in  the  fibres  of  the  superior  and  inferior  laryngeal  nerves, 
especially  in  the  former.  The  impulses  which  arise  in  the  lungs  are  under 
ordinary  circumstances  produced  mechanically  by  the  movements  of  the  lungs, 
although  it  is  believed  by  some  that  the  composition  of  the  gases  in  the  alveoli 
is  an  important  factor.  According  to  the  latter  view,  when  the  lungs  are  in 
the  expiratory  phase  the  accummulation  of  COa  in  the  air-cells  excites  the 
peripheries  of  the  inspiratory  fibres,  thus  giving  rise  to  impulses  which  are 
carried  to  the  inspiratory  portion  of  the  respiratory  centre  and  excite  inspi- 
ration ;  whereas  the  stretching  of  the  lungs  during  inspiration  is  held  to  excite 
the  peripheries  of  the  expiratory  fibres,  generating  impuses  which  are  conveyed 
to  the  expiratory  portion  of  the  expiratory  centre,  causing  expiration.  There 
is,  however,  no  sufficient  evidence  to  lead  us  to  believe  that  the  presence  of 
( '( ).,  in  normal  percentages  influences  in  any  way  either  set  of  fibres.  On  the 
contrary,  the  mechanical  effects  of  the  movements  of  the  lungs  are  of  great 
importance,  as  is  apparent  from  the  fact  that  inflation  excites  active  expi- 
ration,  whereas  aspiration  or  collapse  excites  inspiration;  moreover,  if  the 
movements  of  one  lung  be  prevented  by  occlusion  of  the  bronchi  or  by  free 
opening  of  the  pleural  sac,  the  effects  are  the  same  as  though  the  vagus  of  the 
same  side  were  cut ;  if  now  the  other  nerve  be  severed,  the  results  are  the  same 
as  when  both  nerves  are  cut.  The  movements  of  the  lungs  therefore  generate 
alternate  inspiratory  and  expiratory  impulses,  collapse  causing  inspiratory 
impulses,  and  expansion  causing  expiratory  impulses.  The  inspiratory 
impulses,  however,  not  only  excite  inspiration,  but  concurrently  limit  the 
duration  of  expiration  ;  while  the  expiratory  impulses  excite  expiration  and 
concurrently  limit  inspiration. 

Excitation  of  the  swperwr  laryngeal  nervt  causes  expiratory  stimulation, 
and  there  may  occur  respiratory  arrest  in  the  expiratory  phase.  These  fibres 
are  extremely  sensitive;  and  they  are  of  considerable  physiological  import- 
ance, as  is  illustrated  by  the  fact  that  the  entrance  of  foreign  bodies  into 
the  larynx  during  deglutition  causes  an  immediate  arrest  of  inspiration,  and 
even  a  forced,  spasmodic  expiration.  The  foreign  particles,  coming  in 
contact  with  tin;  keenly  sensitive  fibre-  of  these  nerves,  generate  impulses 
which  arrest  inspiration,  thus  being  prevented  from  being  carried  to  the 
lungs. 

'flic  fibres  of  the  glosso-pharyngeal  nerves  act  similarly.  Their  excitation 
is  followed  by  an  arrest  of  respiration  which  last-  for  a  period  equal  to  that 
occupied  by  about  three  of  the  preceding  respiratory  acts.  The  value  of  such 
an  inhibitory  influence  is  obvious:  During  swallowing  breathing  is  arrested, 
evidently  for  the  purpose  of  preventing  the  aspiration  of  food  and  drink  into 
the  larynx.  This  act  is  purely  reflex,  and  is  due  to  the  excitation  of  fibres  of 
these  nerves  by  the  fluid  or  the  bolus  of  food  after  the  act  of  deglutition  has 
begun.  Such  impulses  flow  to  the  respiratory  centre,  immediately  arresting 
the  inspiratory  discharge'  in  whatever  phase  the  inspiratory  movement    may 


BESPIRA  TION.  463 

happen  to  be.  When  swallowing  has  been  accomplished  the  inhibitory  influ- 
ence is  removed  and  respiration  is  resumed. 

The  inhalation  of  irritating  gases  may  cause  respiratory  arrest  by  exciting 
either  the  sensory  fibres  of  the  trigeminal  nerves  in  the  nose  or  the  pneumo- 
gastric  fibres  in  the  larynx  and  lungs.  Some  gases  affect  the  former,  some 
the  latter,  others  both.  In  the  rabbit,  for  example,  the  introduction  of  tobacco- 
smoke  into  the  lungs  through  a  tracheal  opening  produces  no  effect  upon  the 
respirations,  but  if  injected  into  the  nose  respiration  is  at  once  arrested.  When 
ammonia  is  similarly  introduced  into  the  lungs  the  respirations  may  be  either 
accelerated  or  diminished,  and  may  be  arrested  in  the  inspiratory  or  the  expi- 
ratory phase,  but  when  drawn  into  the  nose  expiratory  arrest  follows.  Some 
irritating  gases  arrest  respiration  in  the  inspiratory  phase,  others  in  the  expi- 
ratory phase.  Odorous  gases  which  are  powerful  and  disagreeable  may  simi- 
larly cause  arrest  by  acting  upon  the  olfactory  nerves.  Excitation  of  the 
splanchnic  nerves  causes  expiratory  arrest;  stimulation  of  the  sciatic  and  sen- 
sory nerves  in  general  usually  increases  the  number  of  respirations,  yet  under 
certain  circumstances  it  may  cause  a  decrease  and  final  arrest  during  expi- 
ration. 

Stimulation  of  the  cutaneous  nerves,  as  by  a  cold  douche,  slapping,  etc., 
causes  primarily  a  tendency  to  an  increase  in  the  number  and  depth  of  the  res- 
pirations, but  finally  causes  cessation  in  the  expiratory  phase.  It  is  stated  that 
excitation  of  these  nerves  is  more  effective  in  causing  respiratory  movements 
than  irritation  of  the  vagi.  The  influence  of  external  heat  is  very  powerful, 
and  is  perhaps  the  most  potent  means,  under  ordinary  circumstances,  of  exciting 
the  respiratory  centre.  The  respiratory  movements  caused  by  cutaneous  irrita- 
tion, are,  however,  of  the  character  of  reflex  spasms  rather  than  of  normal 
movements,  and  when  the  excitation  is  sufficiently  strong  the  movements  may 
be  distinctly  convulsive. 

Finally,  afferent  (intercentral)  fibres  connect  the  brain-cortex,  and  probably 
the  ganglia  at  the  base  of  the  brain,  with  the  respiratory  centres. 

The  Efferent  Respiratory  Nerves. — During  ordinary  respiration  the  only 
efferent  or  motor  nerves  necessarily  involved  are  the  phrenics,  and  certain  other 
of  the  spinal  nerves,  and  the  pneumogastrics.  Section  of  one  phrenic  nerve  causes 
paralysis  of  the  corresponding  side  of  the  diaphragm;  section  of  both  phrenics 
is  followed  by  paralysis  of  the  entire  diaphragm.  So  important  are  these 
nerves  in  respiration  that  in  most  cases  after  section  death  occurs  from  asphyxia 
within  several  hours.  In  such  cases  not  only  is  the  work  <>f  inspiration  thrown 
upon  the  other  inspiratory  muscles,  but  the  effectiveness  of  the  latter  is  greatly 
compromised  by  the  relaxed  condition  of  the  diaphragm,  which  permits  of  its 
being  drawn  into  the  thoracic  cavity  with  each  inspiration,  thus  hindering  the 
expansion  of  the  lungs.  If  section  be  made  of  the  spinal  < •« »r<  1  just  below  the 
exit  of  the  fifth  cervical  nerve,  costal  movements  cease,  l>ut  diaphragmatic  con- 
tractions continue.  The  level  of  the  section  is  just  below  the  origin  of  the  roots 
of  the  phrenics,  so  thai  the  motor  fibres  for  the  diaphragm  arc  left  intact,  but 
the  motor  impulses  which  would  have  gone  out  to  other  inspiratory  muscles 


464  AN   AMERICAN    TEXT-HOOK   OF  PHYSIOLOGY. 

through  the  spinal  nerves  below  the  point  of  section  are  cut  off.  If  the  cord 
be  cul  jusl  below  the  medulla  oblongata  or  above  the  origin  of  the  phrenics, 
both  costal  and  diaphragmatic  movements  immediately  or  very  soon  cease,  but 
respiratory  movements  may  continue  in  the  larynx,  and  when  dyspnoea  occurs 
tiny  may  be  observed  in  the  muscles  of  the  face,  neck,  and  month.  In  rare 
cases,  after  section  at  the  junction  of  the  medulla  oblongata  and  the  spinal  cord, 
respiratory  movements  may  continue  in  the  thorax  and  the  abdomen,  but  these 
instances  are  exceptional  and  the  movements  are  of  the  nature  of  reflex  spasms. 

During  each  respiratory  act  there  flow  to  the  larynx  impulses  which  open 
the  glottis  during  inspiration.  'Fhe  pathway  of  these  impulses  is  through  the 
laryngeal  branches  of  the  vagi,  almost  solely  through  the  recurrent  or  inferior 
laryngeal  nerves.  (See  section  on  the  Physiology  of  the  Voice.)  If  the  pneu- 
mogastrics  are  cut  above  the  origin  of  these  branches,  respiratory  movements 
in  the  larynx  cease,  and,  owing  to  the  paralysis  of  the  laryngeal  muscles,  the 
vocal  cords  are  flaccid,  the  glottis  is  no  longer  widened,  and  thus  great  resist- 
ance is  offered  to  the  inflow  of  air,  causing  difficulty  during  inspiration. 

During  forced  breathing,  besides  the  above  nerves  a  number  of  others  may 
be  involved,  especially  the  spinal  nerves,  which  supply  the  extraordinary  respi- 
ratory muscles  of  the  chest,  abdomen,  pelvis,  and  vertebral  column,  and  the 
facial,  hypoglossal,  and  spinal  accessory  nerves. 

L.  The  Condition  of  the  Respiratory  Centre  in  the  Fetus. 

During  intra-nterine  life  the  child  receives  O  from  and  gives  C02  to  the 
blood  of  the  mother.  No  attempt  is  made  by  the  child  to  breathe,  because  the 
centre  is  in  an  apnoeic  condition,  due  to  a  low  condition  of  irritability  and  to 
the  relatively  large  amount  of  ()  in  the  blood.  The  fetal  blood  contains  a 
larger  percentage  of  haemoglobin  than  the  blood  of  the  mother;  Quinquaud 
has  shown  that  the  fetal  blood  has  a  larger  respiratory  capacity  than  adult's 
blood  ;  and  Regnard  and  Dubois  have  proven  the  same  to  be  true  of  the  calf 
and  the  cow.  Were  it  not  for  these  two  conditions,  the  child  would  continu- 
ally attempt  to  breathe.  While  such  efforts  do  not  occur  under  normal  cir- 
cumstances, they  may  be  present  if  we  interfere  in  any  way  with  the  supply  of 
oxygen,  as  by  pressure  upon  the  umbilical  vessels.  The  child  has  been  seen 
to  make  respiratory  efforts  while  within  the  intact  fetal  membranes.  It  seems 
evident,  therefore,  that  all  that  is  necessary  to  excite  the  respiratory  centre  to 
•activity  is  a  venous  condition  of  the  blood.  /;/  utero,  and  as  long  as  the  child 
is  bathed  in  the  amniotic  fluid,  respiratory  movements  cannot  be  carried  on 
even  though  the  respiratory  centre  be  excited  to  activity,  the  reason  being  that 
with  the  first  movement  of  inspiration  amniotic  fluid  is  drawn  into  the  nasal 
chamber;  the  fluid  acts  as  a  powerful  excitant  to  the  sensory  fibres  of  the 
mucous  membrane,  thus  causing  inhibitory  respiratory  impulses.  From  this 
tact  we  learn  the  practical  application  that  it  is  desirable  immediately  after  birth 
of  a  child,  if  spontaneous  respirations  do  not  immediately  and  effectively  occur, 
t<>  carefully  remove  mucus  or  other  matter  from  the  nose, so  that  the  inhibitory 
influences  generated  by  nasal  irritation  shall  be  discontinued. 


RESPIRATION.  465 

When  the  exchange  of  O  and  C02  is  interfered  with  for  a  long  period,  as 
in  cases  of  prolonged  labor,  the  respiratory  centre  may  become  so  depressed 
that  spontaneous  respirations  do  not  occur  upon  the  birth  of  the  child.  In 
such  a  case  respirations  may  usually  be  initiated  by  irritation  of  the  skin,  as 
by  slapping,  sprinkling  with  iced  water,  etc.  Respirations  may  also  be  carried 
on  successfully  by  artificial  means  (see  p.  446). 

In  utero  the  lungs  are  devoid  of  air;  the  sides  of  the  alveoli  and  of  the 
small  air-passages  are  in  apposition,  although  the  lungs  completely  fill  the 
compressed  thoracic  cavity.  During  the  first  inspiration  comparatively  little 
air  is  taken  into  the  lungs,  because  of  the  force  necessary  to  overcome  the 
adhesion  of  the  sides  of  the  alveoli  and  of  the  smaller  air-tubes,  but  as  one 
inspiration  follows  another  inflation  increases  more  and  more  until  full  disten- 
tion is  accomplished.  The  vigorous  crying  which  so  generally  occurs  immedi- 
ately after  birth  doubtless  is  of  value  in  facilitating  this  expansion.  If  once 
the  lungs  have  been  filled  with  air,  they  are  never  completely  emptied  of  it, 
either  by  volitional  effort  or  by  collapse  after  excision. 

M.  The  Innervation  of  the  Lungs. 

The  nerves  of  the  lungs  are  derived  from  the  pnewmogastrics,  the  sympa- 
thetica, and  the  upper  dorsal  nerves.  Scattered  along  the  paths  of  distribution 
of  these  fibres  are  many  small  ganglia. 

The  Pneumogastric  Nerves. — The  pulmonary  branches  of  the  pneumogas- 
tric  nerves  contain  not  only  fibres  which  convey  impulses  that  affect  the  gen- 
eral characters  of  the  respiratory  movements,  but  other  fibres  that  are  of 
great  importance  to  the  respiratory  mechanism.  Setting  aside  the  effects  on 
the  respiratory  movements  following  section  and  stimulation  of  one  or  of  both 
vagi,  there  are  observed  phenomena  which  are  of  an  entirely  different  character, 
and  which  are  due  to  excitation  or  paralysis  of  certain  other  specific  nerve- 
fibres.  Among  these  fibres  are  efferent  and  afferent  hroncho-conxtrictors  and 
broncho-dilators.  Roy  and  Brown1  found  in  investigations  upon  dogs  that 
stimulation  of  one  vagus  caused  constriction  of  the  bronchi  in  both  Lungs; 
section  of  one  vagus  was  followed  by  expansion  of  the  bronchi  in  the  corre- 
sponding lung,  which  expansion  was  sometimes  preceded  by  a  slight  contraction 
owing  to  the  temporary  irritation  caused  by  the  section;  stimulation  of  the 
peripheral  end  of  the  cut  nerve  caused  a  contraction  of  the  bronchi  in  both 
lungs;  stimulation  of  the  central  end  of  the  cut  nerve  was  followed  by  a  con- 
traction of  the  bronchi  in  both  lungs,  lint  not  so  marked  as  when  the  peripheral 
end  was  stimulated  ;  stimulation  of  sensory  nerves  other  than  the  vagus  rarely, 
and  then  only  to  a  slight  extent,  caused  contraction  ;  atropine  paralyzed  the 
constrictor  fibres ;  nicotine  in  small  doses  had  a  powerful  expansive  effeci  on 
the  bronchi;  after  etherization  stimulation  of  either  the  central  or  the  periph- 
eral end  of  the  cut   pneumogastric  nerve  was  often  followed  by  broncho-dilata- 

1  Journal  of  Physiology,  vol.  6,  1885  (Proceedings  of  the  Physiological  Society,  iii.  p.  xxi.i; 
Einthoven,  Pftiiger's  Archiv  fur  Physiologie,  1892,  Bd.  51,  8.  367 ;  Sandeman,  DuBois-ReymoncT  s 
Archivfur  Physiologie,  1890,  S.  252. 

Vol.  I 30 


466  AN    AMERICAN    TEXT-BOOK   OF    PHYSIOLOGY. 

timi ;  asphyxia  causes  broncho-constriction,  but  not  alter  section  of  the  pneu- 
mogastric  oerves;  after  section  of  both  vagi  it  is  impossible  to  cause  reflex 
broncho-constriction  or  broncho-dilatation;  the  constriction  of  the  bronchi 
may  be  so  great  as  to  reduce  their  calibres  to  one-half  or  one-third,  or  even 
more.  Theabove  results  are  very  instructive,  and  show — (1)  That  broncho- 
constriction  or  broncho-dilatation  can  be  obtained  by  stimulating  the  peripheral 
end  of  the  vagus,  and  that  these  changes  occur  in  the  bronchi  of  both  lungs 
when  only  one  nerve  is  excited,  tints  proving  that  each  nerve  supplies  both 
kinds  of  fibres  to  both  Lungs;  (2)  that  the  same  results  can  be  obtained  by  ex- 
citation of  the  central  end  of  the  cut  nerve,  thus  showing  that  the  pneumogas- 
trics  contain  both  afferent  constrictor  and  afferent  dilator  fibres  ;  (3)  that  reflex 
broncho-constriction  and  broncho-dilatation  cannot  be  produced  after  section 
of  the  vagi,  thus  proving  that  all  of  the  efferenl  fibres  pass  through  the  pneu- 
mogastrics;  (4)  that  asphyxia  and  the  inhalation  of  CO,  cause  broncho-con- 
striction, but  not  after  section  of  the  vagi,  thus  indicating  that  under  these 
circumstances  the  effect-  on  the  bronchi  are  reflex;  (5)  that  certain  poisons 
affect   one  or  the  other  of  these   two  sets  of*  fibre-. 

The  presence  of  efimit  r <i so- motor  fibres  in  the  vagi  has  been  disproved  by 
die  results  of  experiments  by  Bradford  and  Dean,1  and  others.  These  observers 
have  shown,  however,  that  the  vagi  contain  afferent  pressor  fibres,  irritation  of 
which  is  followed  by  constriction  of  the  pulmonary  vessels  that  may  or  may 
nor  be  accompanied  by  constriction  of  the  systemic  vessels,  the  efferent  fibres 
in  this  ease  reaching  the  Lungs  through  the  sympathetic  nerves. 

The  existence  of  trophic  fibres  is  generally  admitted.  After  section  of  one 
pneumogastric  nutritive  changes  immediately  begin  in  the  lung  of  the  corre- 
sponding side,  which  changes  are  manifest  in  the  appearance  of  inflammation 
in  the  middle  and  lower  lobes.  Section  of  both  nerves  is  followed  by  inflam- 
mation in  the  middle  and  lower  lobes  of  both  lung.-. 

The  vagi  contain  sensory  fibres  for  the  larynx,  trachea,  and  lungs,  after  sec- 
tion of  which  fibres  there  i-  an  absolute  loss  of  sensibility  in  these  parts. 

It  is  probable  that  the  vagi  contain  secretory  fibre-  for  the  mucous  glands. 

Tim-  we  find  that  the  pneumogastric  nerves  supply  the  lungs  with  (1) 
afferent  inspiratory  and  expiratory  fibre.-;  (2)  afferent  and  efferent  broncho- 
constrictor  and  h'onclw-dilator  fibre-;  (3)  afferent  pressor  fibres;  (4)  general 
sensory  fibre-;  (5)  trophic  fibre-;  (6)  and  probably  secretory  fibres  for  the 
mucous  glands. 

The  Sympathetic   Nerves.- — The  sympathetics  supply  trophic  and  efferent 
vaso-motor  fibre-.     The  efferenl  vaso-motor  fil>res  pass  from  the  spinal  cord  in 
the  anterior  root-  of  the  second  to  tin-  seventh  dorsal  nerve,  inclusive,  to  join 
the  sympathetics,  thence  through  the  first  thoracic  ganglia  to  the  lung-. 
The  Ganglia. — Nothing  i-  known  of  the  functions  of  the  ganglia. 

1   .fniirnnl  i,f   I'hii.-iohnfii.   I  S'.t  |,   vol.  ]f>,  p.  70. 


VIII.  ANIMAL  HEAT. 


A.   Bodily  Temperature. 

Homothermous  and  Poikilothermous  Animals. — Animal  organisms  are 
divided  as  regards  bodily  temperature  into  two  classes,  homothermous  and 
poikilothermous.  The  temperature  of  homothermous  (warm-blooded)  animals 
is  constant  within  narrow  limits  and  is  not  materially  affected  by  alterations 
of  the  temperature  of  the  medium  in  which  the  organism  lives.  The  tempera- 
ture of  poikilothermous  (cold-blooded)  animals  normally  ranges  from  a  frac- 
tion of  a  degree  to  several  degrees  above  that  of  the  surrounding  medium,  and 
under  ordinary  circumstances  rises  and  falls  with  corresponding  changes  of  sur- 
rounding temperature.  The  old  terms  warm-blooded  and  cold-blooded  imply 
that  the  difference  between  the  two  classes  is  one  of  absolute  temperature,  the 
former  having  a  temperature  higher  than  the  latter,  and  although  this  is  gener- 
ally the  case  it  is  not  necessarily  so.  For  instance,  Landois  has  recorded  thai  a 
frog  (cold-blooded)  in  water  at  a  temperature  of  20.6°  C.  had  a  temperature  of 
about  20.7°  C,  and  that  when  the  water  was  at  41°  C.  his  temperature  rose  to 
about  38°  C,  which  is  higher  than  the  mean  temperature  of  man  (warm- 
blooded). The  temperature  of  cold-blooded  animals  may,  therefore,  be  higher 
than  that  of  warm-blooded  animals.  The  difference  therefore  is  relative  and 
not  absolute,  the  chief  distinguishing  feature  being  that  the  temperature  of 
homothermous  animals  is  practically  constant,  while  that  of  poikilothermous 
animals  fluctuates  with  the  temperature  of  the  medium  in  which  (lie  organism 
exists.  The  class  of  homothermous  animals  includes  mammals  and  birds  ;  and 
that  of  poikilothermous  animals,  fish,  reptiles,  amphibia,  and  invertebrates. 

Temperatures  of  Different  Species  of  Animals. — The  temperature  of 
every  animal  varies  in  different  parts  of  the  organism,  so  that  in  making  com- 
parisons it  is  necessary  that  the  observations  be  made  in  the  same  region  of  the 
body  of  the  different  individuals,  and  as  far  as  possible  under  the  same  internal 
and  external  conditions.  As  a  rule,  rectal  temperatures  are  preferable,  and 
in  making  them  it  is  especially  desirable,  in  order  to  ensure  practical  accuracy, 
that  the  bulb  of  the  thermometer  be  inserted  well  into  the  pelvis,  and  that  it 
does  not  rest  within  a  mass  of  Cecal  matter.  The  depth  to  which  the  bull)  is 
inserted  is  also  of  importance,  as  shown  by  Kinkier,  who  (bund  in  experiments 
on  a  guinea-pig  that  the  temperature  was  36.1°  C.  :it  a  depth  of  2.5  centimeters, 
38.7°  C.  at  6  centimeters,  and  38.9°  C.  at  9  centimeters.  The  following  records 
of  mean  bodily  temperature  of  various  species  have  been  derived  from  various 
sources,  chiefly  from  the  compilations  of  (iavarret  : 

407 


168  AN  AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

Mammals.  Birds.  Reptiles  and  Fish.1 

Centigrade.  Centigrade.  |  Centigrade. 

Mouse 41.1°  Minis     ....        11.03°  Frog 0.32-2.44° 

Sheep 37.3-40.5°    Duck 42.50-43.90°    Snakes 2.5-12.0° 

\pe 35.5-39.7°    Goose 41.7° 

Rabbit 39.6-40.0°    Gull 37.8° 

Guinea-pig.    .    .    .38.4-39.0°    Guinea 43.90° 

Dog 37.4-39.6°  \  Turkey 42.70° 

Cat 38.3-38.9°    Sparrow     ....  39.08-42.10° 

Chicken    ....  43.0° 
Crow 41.17° 


Horse 36.8-37.5° 

Rat 38.8° 


Ox 37.5° 

Ass 36.95c 


Fish 0.5-3.0° 

Invertebrates.1 

Crustacea 0.6° 

(Vphalopods     -    .    .0.57° 

Medusae 0.27° 

Polyps 0.21° 

Molluscs 0.46° 


The  Temperature  of  the  Different  Regions  of  the  Body. — The  quanti- 
ties of  heat  produced  and  dissipated  by  different  parts  of  the  economy  vary, 
consequently  there  must  continually  be  a  transmission  of  heat  from  the  warmer 
to  the  cooler  parts  to  establish  throughout  the  organism  an  equilibrium  of  tem- 
perature. Heat  is  distributed  by  direct  conduction  from  part  to  part,  but  prob- 
ably chiefly  by  the  circulating  blood  and  lymph.  These  means  of  distribution 
are,  however,  not  sufficiently  active  to  establish  a  uniform  temperature.  Thus 
we  fiud  that  the  internal  parts  of  the  body  have  a  higher  temperature  than  the 
external  parts  ;  that  some  internal  organs  are  considerably  warmer  than  others  ; 
that  every  organ  is  warmer  when  active  than  when  at  rest ;  that  the  tempera- 
ture varies  in  different  regions  of  the  surface  of  the  body,  etc.  The  following 
figures  by  Kunkel2  instance  some  of  these  differences,  the  temperature  of  the 
room  being  20°  C. : 

Centigrade.  I  Centigrade. 

Forehead 34.1c-34.4°    Sternum 34.4° 

Cheek  under  the  zygoma     ....  34.4°  lVetorales 34.7° 

Tip  of  ear 28.8°  Right  iliac  fossa 34.4° 

Back  of  hand 32.5°-33.2°    Left  iliac  fossa 34.6° 

Hollow  of  the  hand  (closed)    .    .    .  34.8°-35.1°    Os  sacrum 34.2° 


Hollow  of  the  hand  (open)  ....  31.4°-34.8° 

Forearm 33.7° 

Forearm  (higher) 34.3° 


Eleventh  rib  (back) 34.5° 

Tuberosity  of  ischium 32.0° 

Upper  part  of  thigh 34.2° 

(  all 33.6° 


The  temperature  of  the  skin  is  higher  over  an  artery  than  at  some  distance 
from  it  ;  it  is  higher  over  muscle  than  over  sinew  ;  it  is  higher  over  an  organ 
in  activity  than  when  at  resl  ;  it  i-  higher  in  the  frontal  than  in  the  parietal 
region  of  the  head,  and  on  the  left  side  of  the  head  than  on  the  right,  etc. 

Temperature  observations  arc  usually  made  in  the  rectum,  in  the  mouth 
under  the  tongue,  in  the  axilla,  and  in  the  vagina,  the  rectum  being  preferable, 
although  in  the  human  being  the  temperature  is  usually  obtained  in  the  mouth 
and  axilla.  In  the  same  individual  when  records  are  taken  simultaneously  in 
all  four  regions  appreciable  differences  will  be  noted.  The  temperature  in  the 
axilla  is,  according  to  Hunter  37.2°  C,  to  Davy  37.3°  C.,to  Wunderlich  36.5° 
to  37.25°  C.  (mean  37.1°  ('.).  to  Liebermeister  36.89°  C,  to  Jurgensen  37.2°  C, 

1  Temperatures  above  that  of  the  surrounding  medium. 

2  Zeitsi-hrift  fur  Biologic,  L889,  Bd.  25,  S.  o9-73. 


ANIMAL  HEAT.  469 

and  to  Jaeger  37.3°  C.  The  mean  axillary  temperature  may  be  put  down  as 
being  about  37.1°  C.  (98.8°  F.),  the  normal  limits  being  36.25°  to  37.5°  C. 
(97.2°  to  99.5°  F.)  The  temperature  in  the  mouth  is  about  0.2°  to  0.5°  C. 
higher  than  in  the  axilla,  in  the  rectum  from  0.3°  to  1.5°  C.  higher,  and  in  the 
vagina  from  0.5°  to  1.8°  C.  higher.1 

The  temperature  of  different  tissues  varies.  Davy,  as  results  of  observa- 
tions on  a  fresh-killed  sheep,  gives  the  temperature  of  the  brain  as  about  40° 
C.j  of  the  left  ventricle  41.67°  C. ;  of  the  right  ventricle  41.11°  C.;  of  the 
liver  41.39°  C.  ;  of  the  rectum  40.56°  C.  According  to  Bernard,  the  liver  is 
the  warmest  organ  in  the  body,  and  then  the  following  in  the  order  named — 
brain,  glands,  muscles,  and  lungs. 

The  temperature  of  the  blood  varies  considerably  in  different  vessels.  In 
the  carotid  it  is  from  0.5°  to  2°  C.  higher  than  in  the  jugular  vein;  in  the 
crural  artery,  from  0.75°  to  1°  C.  higher  than  in  the  corresponding  vein  ;  in 
the  right  side  of  the  heart  about  0.2°  C.  higher  than  in  the  left;  in  the  hepatic 
vein  0.6°  C.  higher  than  in  the  portal  vein  during  the  intervals  of  digestion, 
and  as  much  as  1.5°  to  2°  C.  or  more  during  periods  of  digestion  ;  the  venous 
blood  coming  from  internal  organs  is  warmer  than  the  arterial  blood  going  to 
them,  but  the  blood  coming  from  the  skin  is  cooler  than  that  going  to  it ;  the 
blood  coming  from  a  muscle  in  a  state  of  rest  is  about  0.2°  C,  and  during 
activity  as  much  as  0.6°  to  0.7°  C,  warmer  than  that  supplied  to  the  muscle. 
The  mean  temperature  of  the  blood  as  a  whole  is  about  39°  C.  (102°  F.);  of 
venous  blood  about  1°  C.  (1.8°  F.)  lower  than  of  arterial  blood.  The  warm- 
est blood  in  the  body  is  that  coming  from  the  liver  during  the  period  of  diges- 
tion; the  coolest  blood  is  that  coming  from  the  tips  of  the  ears  and  nose  and 
similarly  exposed  parts. 

Conditions  affecting-  Bodily  Temperature. — The  mean  temperature  of 
the  body  is  subjected  to  variations  which  depend  chiefly  upon  age,  sex,  consti- 
tution, the  time  of  day,  diet,  activity,  season  and  climate  (surrounding  tem- 
perature), the  blood-supply,  disease,  drugs,  the  nervous  system,  etc. 

The  temperature  of  a  new-born  child  (37.86°  C.)  is  from  0.1°  to  0.3°  C. 
higher  than  that  of  the  vagina  of  the  mother;  it  falls  about  1°  < '.  during  the 
first  few  hours  after  birth,  and  then  ii>cs  within  the  next  twenty-four  hours  to 
about  37.4°  to  37.5°  C  The  mean  temperature  of  an  infant  a  day  or  two 
old  is  about  37.4°  C.  It  very  slowly  sinks  until  full  growth  is  attained,  when 
the  normal  mean  temperature  of  adult  life  is  reached  (37.1°  C),  a  standard 
which  is  maintained  until  about  the  age  of  forty-five  or  fifty,  when  it  declines 
until  about  the  age  of  seventy  (36.8°  C),  and  then  slowly  rises  and  approaches 
in  very  old  people  (eighty  to  ninety  years)  the  temperature  of  very  young 
infants  (37.4°  C).  It  is  important  to  observe  that  during  the  early  weeks  "I 
life  the  temperature  may  undergo  considerable  variation-,  and  thai  it  is  readily 
affected  by  bathing,  exposure,  crying,  pain,  sleep,  etc,  and    by    many   circum- 

1  The  average  figures  of  the  mean  daily  temperatures  obtained  from  tin-  records  of  ;i  num 
ber  of  investigators  are,  mouth,  o<5.S7° ;  axilla,  3d. 94°  ;  ami  rectum,  37.02°.  The  mean  figures 
for  the  twenty-four  hours  are  in  each  rase  about  0.2°  less. 


470  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

stances  which  have  little  or  absolutely  no  influence  upon  the  temperature  of 
the  adult. 

The  mean  temperature  of  the  female  is  said  to  be  slightly  lower  than  that 
of  the  male  In  observations  on  children  Sommer  noted  a  difference  of  0.05° 
('..  and  Fehlinga  difference  of  0.33°  C. 

Individuals  with  vigorous  constitutions  have  a  somewhat  higher  temper- 
ature than  those   who  are   weak. 

Records  obtained  by  various  European  investigators  indicate  that  the  bodily 
temperature  is  subjected  to  regular  diurnal  variations.  The  limits  of  variation 
in  health  are  from  1°  to  2°  C.  The  maximum  temperature  observed  is  usu- 
ally from  5  to  8  p.  If.  (mean,  about  7  p.  m.)  ;  the  minimum,  from  2  to  6  a.  m. 
(mean,  about  4  a.  M.J.  Carter's1  experiments  on  rabbits,  cats,  and  dogs  show 
that  rhythmical  temperature-changes  occur  in  these  animals  which  agree  with 
those  noted  by  Jurgensen  in  man.  This  same  rhythm  is  stated  to  occur  during 
fasting,  so  that  the  ingestion  and  the  digestion  of  food  cannot  he  claimed  to 
account  for  it;  moreover,  it  is  present  in  fever  and  not  disturbed  by  muscular 
activity  and  by  cold  baths.  If  an  individual  works  at  night  and  sleeps  during 
the  day,  thus  reversing  the  prevailing  custom,  the  temperature  curve  is  more 
or  less  modified,  but,  according  to  Mosso,2  not  reversed  as  stated  by  Krieger.3 
Chclmonski  found,  however,  in  old  persons  that  the  temperature  variations 
are  not  uncommonly  inverted,  being  higher  in  the  morning  and  lower  in  the 
evening. 

Insufficient  diet  causes  a  lowering  of  the  temperature;  a  liberal  diet  tends 
to  cause  a  rise  slightly  above  the  normal  mean,  especially  during  forced  feeding 
or  when  the  food  is  particularly  rich  in  fats  and  carbohydrates.  There  is  a 
rise  during  digestion  which  is  usually  slight,  but  it  may  reach  0.2°  or  0.3°,  the 
increase  being  due  chiefly  to  the  activity  of  the  intestinal  muscles  (see  p.  431). 
Although  considerably  more  heat  is  produced  during  the  periods  of  digestion 
than  during  the  intervals,  the  excess  is  dissipated  almost  as  rapidly  as  it  is 
formed,  so  that  but  little  heat  is  permitted  to  accumulate  and  thus  cause  a  rise 
of  temperature.  Hot  drinks  and  solids  tend  to  augment,  and  cold  drinks  and 
solids  to  lower  bodily  temperature.  In  the  nursing  child  I  temme  found  that  the 
n.tal  temperature  sinks  during  the  first  half-hour  after  taking  food,  then  rises 
during  the  next  Bixty  to  ninety  minutes  to  a  point  from  0.2°  to  0.8°  C.  higher 
than  the  temperature  before  feeding,  and  falls  again  during  the  next  thirty  to 
sixty  minute-. 

All  condition-  which  increase  metabolic  activity  are  favorable  to  an  increase 
of  temperature.  Thus,  during  the  activity  of  the  brain,  glands,  muscles,  etc., 
more  heat  is  produced  than  when  the  tissues  are  at  rest;  indeed,  so  abundant 
is  heat-production  during  severe  muscular  exercise  that  the  temperature  of  the 
body  may  rise  a-  much  as  <>..~,°  to  1.5°  C.  (l°to  2.7°  F.).  During  sleep  the 
temperature  falls  from  <)..'5°  to  0.9°  C.  or  more  in  young  children. 

:  Journal  of  Nervous  and  Mental  Diseases,  1890,  vol.  xvii.  p.  782. 
-  Archives  it<ili>„m  <  ,U  biologic,  L887,  t.  viii.  p.  177. 
3  Zeilsckriftfilr  Biologic,  1869,  Bd.  \.  S.  479. 


'ANIMAL   HEAT.  471 

During  the  summer  the  mean  bodily  temperature  is  from  0.1°  to  0.3°  C. 
higher  than  during  the  winter.  In  warm  climates  it  is  about  0.5°  C.  higher 
than  in  eold  climates,  but  the  difference  is  not  due  to  race,  since  it  is  observed 
in  individuals  who  have  changed  their  habitations  from  one  climate  to  another. 
Continued  exposure  to  excessively  high  or  low  temperatures  is  inimical  to 
Jife.  Exposure  in  dry  air  at  a  temperature  of  100°  to  130°  C.  may  cause 
the  bodily  temperature  to  increase  as  much  as  1°  to  2°  C.  within  a  few  minutes, 
and  the  temperature  may  rise  so  rapidly  as  to  cause  fatal  symptoms  within  ten 
or  fifteen  minutes.  A  hot  moist  air  is  far  more  oppressive  and  dangerous  than 
hot  dry  air. 

Baths  exercise  a  potent  influence  on  bodily  temperature,  hot  baths  increasing 
and  cold  baths  decreasing  it.  The  effect  of  a  cold  bath  is  less  if  it  follows  a 
hot  bath.  Thus  Dill '  found  that  his  morning  temperature  varied  from  33.7° 
to  36.6°  C,  after  a  hot  bath  (40°-41°  C.)  it  rose,  in  one  instance,  as  high  as 
39.5°  C,  and  after  a  cold  bath  it  remained  at  37°  C.  When,  however,  the 
hot  bath  was  omitted  the  cold  bath  reduced  the  temperature  to  35.4°  C.  Bal- 
jakowski2  has  recorded  some  very  interesting  results  which  show  that  the  local 
application  of  heat  causes  the  bodily  temperature  to  sink  and  the  cutaneous 
temperature  of  the  part  experimented  upon  to  rise.  The  experiments  were 
conducted  on  young  men,  whose  arms  and  legs  were  encased  in  hot  sand  at  a 
temperature  of  55°  C.  When  the  arm  was  used  the  axillary  temperature  sunk 
an  average  of  0.13°  C.  during  the  bath  and  subsequently  0.24°  C,  the  corre- 
sponding records  of  average  rectal  temperature  being  0.23°  and  0.31°  C.  In 
case  of  the  leg  bath  the  corresponding  records  were  axillary  0.06°  and  0.32° 
C. ;  and  rectal  0.21°  and  0.25°  C.  The  cutaneous  temperature  of  the  limb 
experimented  upon  increased  materially,  the  average  rise  varying  from  0.73° 
to  1.20°  C,  according  to  the  part  of  the  limb.  Long-continued  severe  exter- 
nal cold  may  prove  fatal,  but  this  is  not  necessarily  due  to  the  effect  on  bodily 
temperature,  for  Milne- Edwards3  has  shown  that  rabbits  die  within  five  or  >ix 
days  when  exposed  to  a  temperature  of  —10°  to  -15°  C,  without  the  bodily 
temperature  falling  more  than   1°  C. 

There  is  a  general  relationship  between  the  frequency  of  the  heart's  beat  and 
the  bodily  temperature,  especially  in  fever.  Barensprung  noted  such  a  coinci- 
dence between  the  diurnal  variations  of  the  pulse  and  bodily  temperature;  and, 
in  fever,  Aiken  found  that  for  each  increase  of  0.55°  C.  (1°  F.)  above  the  mean 
normal  temperature  the  pulse-rate  was  increased  about  ten  beats  per  minute. 
But  the  variations  in  the  two  do  not  always  correspond  either  quantitively  or 
qualitatively.  Liebermeister  found  in  man  that  for  a  rise  of  each  degree  from 
37°  to  42°  C.  the  increase  in  the  pulse-rate  was  12.6,  8.6,  8.7,  11.5,  and  27.5 
beats  per  minute  respectively.  Beljakowski's 4  experiments  show  that  the 
bodily  temperature  may  fall  and  the  pulse-rate  rise — in  one  set  of  experiments 
the  rectal  temperature  falling  on  an  average  0.23°  C.  and  the  pulse  increasing 

1  British  Mrihral  J.nrnal,  lN'.HI,  vol.  i.  ]).  1136. 

2  Vratch,  1889,  p.  436;  PtovmcM  Medical  Journal,  1890,  i>.  113. 

3  Comptes  rendus  de  la  Soc.  dc  Bioloi/ie,  1891,  t.  1 12,  pp.  201-  205.  *  Lor.  rit. 


472  AN    AMERICAN   TEXT-BOOK    OF  PHYSIOLOGY. 

on  an  average  6.85  beats  per  minute.  After  the  local  hot  bath  the  temperature 
remained  subnormal,  and  the  heart-beats  became  less  frequent,  and  finally  were 
mi  an  average  from  2.7  to  3.1  beats  per  minute  less  than  the  normal  rate. 

More  important,  however,  than  the  pulse-rate  is  the  effect  of  the  amount 
of  blood  supplied  to  any  given  part  of  the  body.  The  mere  lowering  or  rais- 
ing of  the  arm  is  sufficient  to  alter  the  blood-supply  to  the  part;  thus  Romer 
found  that  keeping  the  arm  elevated  for  five  minutes  was  sufficient  to  reduce 
the  temperature  of  the  hand  0.19°  C,  and  that  if  the  period  was  doubled  the 
fall  amounted  to  0.38°  C.  Compression  of  the  veins  of  the  arm  may  diminish 
the  temperature  of  the  hand  as  much  as  0.25°  to  2.45°  C,  while  compression 
of  the  brachial  artery  may  cause  a  fall  of  2.4°  within  fifteen  minutes.  A  larger 
supply  of  blood  to  the  cutaneous  surface  increases  cutaneous  temperature  and 
tends  to  decrease  internal  temperature,  while  a  lessened  supply  causes  the 
opposite  effect-. 

In  abnormal  conditions  the  temperature  may  be  increased  or  decreased  :  in 
cholera,  diabetes,  and  in  the  last  stages  of  insanity,  it  may  be  lowered  6°  or 
8°  C.  or  even  more.  In  fever  it  is  increased,  usually  ranging  between  37.5° 
and  41.5°  C.  (99.4°  and  106.7°  F.),  but  in  very  rare  cases  it  may  reach  44°  to 
45°  C.  (111°  to  113°  F.)  just  before  death.  A  temperature  of  42.5°  C. 
(108.5°  F.)  maintained  for  several  hours  is  almost  inevitably  fatal.  In  frogs, 
the  highest  temperature  consistent  with  life  for  any  length  of  time  is  below 
40°  C. ;  in  birds,  from  48°  to  50°  C,  and  in  dogs,  from  43°  to  45°  C.  Ex- 
ceptional cases  are  on  record  of  people  having  survived  extraordinarily  high 
or  low  bodily  temperature,  Richet  having  reported  one  in  which  the  tempera- 
ture several  times  was  46°  C.  (114.8°  F.),  while  Teale  records  an  axillary  tem- 
perature of  50°  C.  (122°  F.)  in  an  hysterical  (?)  woman.  Frantzel  noted  a 
temperature  of  24.6°  C.  (76.2°  F.)  in  a  drunken  man,  and  Kosiirew  a  temper- 
ture  of  26.5°  C.  (79.7°  F.)  in  a  man  having  a  fractured  skull. 

Bodily  temperature  may  be  variously  influenced  by  drugs  and  other  sub- 
stances, micro-organisms,  etc.  Some  increase  it,  others  decrease  it,  others  are 
without  any  marked  influence,  while  others  exert  primary  and  secondary 
actions.  Among  those  which  increase  bodily  temperature  are  cocain,  atropin, 
strychnin,  brucin,  caffein,  veratrin,  etc.,  and,  as  shown  by  Krehl1  and  others,  a 
large  number  of  other  organic  substances  and  micro-organisms.  Temperature 
is  decreased  by  anaesthetics,  morphin  and  other  hypnotics,  quinin,  various 
antipyretics,  large  doses  of  alcohol,  etc. 

A.mong  the  most  important  of  the  conditions  which  affect  bodily  tempera- 
ture are  disturbances  of  the  nervous  system.  Injury  or  irritation  of  almost 
any  part  of  the  nerve-centres  and  of  certain  nerves  may  give  rise  directly  or 
indirectly  to  alterations  of  temperature,  and  there  are  some  parts  which  are 
very  sensitive  in  this  respeet,  especially  certain  areas  of  the  brain  cortex,  the 
striated  bodies,  the  pons  Varolii,  the  spinal  bulb,  and  the  cutaneous  nerves. 
The  results  of  injury  or  stimulation  of  these  as  well  as  of  other  parts  will 
be  considered  later  on  (p.   193). 

1  Archir  fur  experimentelle  Pathologie  und  Pharmakologi&,  1895,  Bd.  35,  S.  222-268. 


ANIMAL   HEAT.  473 

Temperature-regulation. — The  fact  that  during  life  the  organism  is  con- 
tinually producing  and  losing  heat,  and  that  the  bodily  temperature  of  homo- 
thermous  animal  is  maintained  at  an  almost  uniform  standard,  notwithstanding 
considerable  mutations  of  surrounding  temperature,  renders  it  evident  that 
there  exists  an  important  mechanism  whereby  the  regulation  of  the  relations 
between  heat-production  and  heat-dissipation  is  effected.  It  must  be  evident 
that  when  the  variations  in  heat-production  and  heat-dissipation  balance,  bodily 
temperature  must  remain  unaltered,  and  that  if  the  changes  in  one  exceed 
those  in  the  other  the  temperature  rises  or  falls,  depending  upon  whether  more 
or  less  heat  is  produced  than  is  dissipated.  It  does  not  follow  that  because 
heat-production  is  increased  the  bodily  temperature  must  similarly  be  affected, 
since  heat-dissipation  may  be  increased  to  the  same  extent  and  thus  effect  a 
compensation.  Therefore  an  alteration  in  heat-production  or  in  heat-dissipation 
by  no  means  implies  that  the  temperature  must  be  affected.  Moreover,  when 
the  temperature  is  increased  or  diminished  the  change  may  be  caused  by 
various  alterations  in  the  quantities  of  heat  produced  or  lost,  singly  or  com- 
bined, and  the  temperature  may  remain  constant  even  when  both  processes  are 
materially  affected.  Thus,  the  temperature  remains  constant  when  both  heat- 
production  and  heat-dissipation  are  normal,  and  when  both  are  increased  or 
decreased  to  the  same  extent.  The  temperature  is  increased  when  heat-pro- 
duction is  normal  and  heat-dissipation  diminished ;  when  both  heat-production 
and  heat-dissipation  are  diminished,  but  when  heat-production  is  diminished 
to  a  less  extent  than  heat-dissipation  ;  when  heat-production  is  increased  and 
heat-dissipation  remains  normal;  when  both  heat-production  and  heat-dissipa- 
tion are  increased,  but  when  heat-production  is  increased  to  a  greater  extent 
than  heat-dissipation  ;  and  when  heat-production  is  increased  and  heat-dissipa- 
tion is  diminished.  The  temperature  is  diminished  when  heat-production  is 
normal  and  heat-dissipation  is  increased ;  when  heat-production  is  diminished 
and  heat-dissipation  remains  normal;  when  heat-production  and  heat-dissipa- 
tion are  diminished,  but  when  heat-production  is  diminished  to  a  greater  extent 
than  heat-dissipation ;  when  heat-production  is  diminished  and  heat-dissipa- 
tion is  increased ;  and  when  both  heat-dissipation  and  heat-production  are 
increased,  but  when  heat-production  is  increased  to  a  less  extent  than  heat- 
dissipation. 

It  is  generally  regarded  by  clinicians  that  bodily  temperature  varies  directly 
with  heat-production — that  is,  that  a  rise  means  increased  production,  and  a 
fall  diminished  production ;  but  the  fallaciousness  of  such  a  conclusion  must 
be  apparent.  It  may,  however,  be  accepted  as  a  fact  that  in  fever,  as  a  rule, 
an  increase  of  bodily  temperature  is  a  concomitant  of  increased  heat-produc- 
tion, and  diminished  temperature  of  diminished  heat-production;  bftl  it  must 
also  be  observed  that  pyrexia,  although  generally  due  to  increased  heat- 
production,  may  also  be  due  partly  or  wholly  to  diminished  heat-dissipation. 
It  is  obvious,  therefore,  that  temperature  variations  simply  show  that  the 
balance  between  heat-production  and  heat-dissipation  is  disturbed,  without 
positively  indicating  how  the  processes  of  heat-production  and  heat-dissipation 
are  affected. 


474  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

The  mechanism  concerned  in  the  adjustment  of  the  relations  between  heat- 
production  and   heat-dissipation   will   be  considered   under   another   heading 

(p.  495). 

B.  Income  and  Expenditure  of  Heat. 

Broadly  speaking,  the  source  of  animal  heat  is  in  the  potential  energy  of 
organic  food-stuffs — so  little  relatively  being  obtained  from  the  heat  of  warm 
food  and  drink  and  directly  from  external  sources,  such  as  the  sun's  rays, 
that  these  sources   may  be  disregarded. 

The  researches  of  Rubner1  have  clearly  shown  that  chemical  changes  in 
the  body  constitute  the  source  of  animal  heat.  He  made  estimations  of  the 
amount  of  heat  that  should  be  formed  in  the  body  as  indicated  by  the  ex- 
change  of  ingesta  and  egesta,  and  also  determined  by  direct  calorimetry  (see 
below)  the  heat  production  in  dogs  under  conditions  of  fasting  and  varying 
diet.  The  results  in  the  two  cases  are  strikingly  close,  as  will  be  observed 
from  the  following  table: 

,-      re         r,  Quantity  of  heat      ^ Vhv^    Per  cent,  dlf- 

Condition  of  dog.  ^  calculated.  Staeter.  ference. 

Fasting 1193.7  calories  1180.1  calories  —1.42 

Diet  of  Fat 1510.1       "  1495.3       "  -0.97 

"       Meat  and  Fat 3238.9       "  3223.2       "  -  0.42 

«        Meat 3515.3       "  3523.1       "  +0.43 

These  figures,  which  are  in  so  close  accord,  are  substantiated  in  their  correct- 
aess  and  import  by  the  results  obtained  by  Laulanie2  in  studies  on  guinea- 
pigs,  rabbits,  ducks,  and  dogs. 

This  potential  energy  of  food  may  be  converted  into  heat  directly  or  indi- 
rectly: directly,  as  an  immediate  result  of  chemical  decomposition;  and  in- 
directly, by  mechanical  movements,  such  as  muscular  contraction,  the  flow 
of  the  blood,  the  friction  of  the  joints,  etc.  About  90  percent,  of  the  heat 
of  the  organism  results  directly  from  chemical  decompositions,  and  about  10 
per  cent,  results  indirectly  from  mechanical  movements.  The  potential 
energy  of  the  food  is  transformed  into  kinetic  energy  (heat  and  work)  essen- 
tially by  processes  of  oxidation.  The  energy-yielding  food-stuffs  enter  the 
body  in  the  form  of  proteids,  fats,  and  carbohydrates,  due  proteid  is  broken 
up  into  urea,  C02J  I  L<>,  and  various  extractives;  and  the  fats  and  carbo- 
hydrates into  C02  and  IIJ).  During  these  oxidative  processes,  by  which  the 
potential  energy  of  the  molecules  is  transformed  into  kinetic  energy,  the 
total  amount  of  energy  evolved  by  the  complete  oxidation  of  a  given  amount 
of  any  substance  is  the  same  whether  the  processes  are  carried  at  once  to  the 
final  stages,  that  is,  to  the  final  disintegration  products,  or  whether  they  pass 
through  an  Indefinite  number  of  intermediate  stages,  provided  that  the  final 
product  or  products  are  the  same.  In  other  words,  the  amount  of  heat 
evolved  by  the  oxidation  of  1  gram  of  proteid  into  urea,  C02,  and  II.O  is 
the  same  when  the  molecule  is  oxidized  immediately  into  these  substances  as 
when  tin'  decomposition  is  carried  through  a  number  of  intermediate  stages. 
1  Zeilschrift  J.  Biologic,  1893,  Bd.  xxx.  S.  73.  *  Archives  <!<■  Physiologie,  1898,  p.  748. 


ANIMAL   HEAT.  47.") 

Income  of  Heat. —  Since  the  energy-yielding  food-stuffs  are  essentially 
proteids,  fats,  and  carbohydrates,  and  composed  of  C,  II,  O,  and  X,  and  since 
the  products  of  their  disintegration  arc  essentially  urea,  0O2,  and  H20,  the 

amount  of  energy  yielded  by  the  oxidation  of  the  food-stuffs  can  readily  be 
determined  if  we  know  the  quantity  and  quality  of  the  food  and  excreta. 
Since  the  energy  of  the  organism  is  manifested  essentially  in  the  form  of 
heat  and  work,  and  as  under  ordinary  circumstances  but  a  fraction  of  it  is 
manifested  as  work,  we  may  in  making  this  estimate,  as  a  matter  of  con- 
venience, consider  that  the  total  available  energy  of  the  food  appears  in  the 
form  of  heat. 

The  income  of  energy  has  been  estimated  by  determining — (1)  the  quan- 
tity of  oxygen  consumed  ;  (2)  the  amounts  of  ( '  and  II  that  are  oxidized  in 
the  body  into  C02  and  H20 ;  (3)  the  quantity  and  quality  of  the  food  con- 
sumed in  the  body  and  the  products  resulting  from  their  decomposition,  and 
the  energy  yielded  by  the  oxidation  of  the  same  substances  outside  the  body 
when  they  are  decomposed  into  the  same  residual  products  as  appear  in  the 
body  ;  (4)  the  quantity  of  heat  produced,  by  the  aid  of  a  calorimeter,  the 
individual  being  kept  quiet  so  that  as  little  as  possible  of  the  energy 
expended  appears  as  work.  The  third  method  is  a  method  of  indirect 
calorimetrv,  and  the  fourth  method  that  of  direct  calorimetry,  or,  briefly, 
calorimetry. 

The  first  two  methods  have  fallen  into  disuse.  According  to  the  third 
method,  it  is  necessary  that  we  know  the  kind  and  quantity  of  food  consumed, 
the  final  products  of  disintegration,  and  the  quantity  of  energy  evolved  by  the 
conversion  of  each  of  the  food-stuffs  to  its  normal  residual  substances.  As  the 
basis  of  these  calculations  we  have  the  fact  that  during  the  complete  oxidation 
of  anv  given  substance  a  definite  amount  of  energy  is  given  off,  and  that  when 
the  oxidation  is  but  partial  only  a  portion  of  energy  is  evolved,  the  proportion 
being  in  accordance  with  the  stage  of  oxidation.  The  complete  oxidation  of 
1  gram  of  proteid  yields  5778  calories;  of  1  gram  of  fat,  9312  calories  ;  and 
of  1  gram  of  carbohydrate,  4116  calories  (see  Potential  Energy  of  Food,  p. 
364).  If  these  substances  be  completely  oxidized  in  the  body,  the  amount  of 
energy  evolved  will  be  the  same  as  though  the  oxidation  occurred  outside 
of  the  body,  provided  that  the  final  products  are  the  same  in  both  cases.  As 
far  as  fats  and  carbohydrates  are  concerned,  we  are  justified  in  assuming  that 
they  are  completely  oxidized  in  the  body  into  COa  and  H2Oj  but  the  proteids, 
as  already  pointed  out,  undergo  only  partial  oxidation,  each  gram  yielding 
about  one-third  of  a  gram  of  urea.  The  results  of  experiments  -how  that 
each  gram  of  urea  contains  potential  energy  equivalent  to  l!o'J"»  calories,  and 
since  each  gram  of  proteid  yields  one-third  of  a  gram  of  urea,  representing 
841  calories,  each  gram  of  proteid  yields  theoretically  to  the  organism  onl\ 
4937  calories.  The  available  energy  from  the  proteid  would,  therefore,  be 
equivalent  to  the  total  amount  of  energy  derivable  from  the  complete  oxida- 
tion nf  the   proteid   minus  the  amount    represented  in  the   urea.      Practically, 


476  AN    AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

according  to  the  experiments  of  Rubner,  each  gram  of  proteid  is  estimated  to 

yield  41D0  calorics.  With  those  facts  in  view  it  is  a  simple  matter  to  deter- 
mine the  total  income  of  energy,  should  the  diet  he  known.  Thus,  if  the 
diel  consists  of  L20  grams  of  proteids,  90  grams  of  fat,  and  330  of  carbo- 
hydrates, the  absolute  and  available  amounts  of  energy  ingested  are — 

Grams.               Calories.  Calories. 

Proteids      120         x         .->77s  693,3ti0 

Fats 90         x         9312  837,080 

Carbohydrates 330         x         411G  1,358,280 

2,888,720 

Dedmt  the  proteid  energy  in  40  grams  of  urea,  40x2523=  100,920 

Total  daily  heat-production 2,787,800 

This  is  assuming  that  the  entire  quantity  of  proteids,  fats,  and  carbohydrates 
is  digested,  absorbed  and  ultimately  broken  down  into  0O2,  H20,  and  urea. 
This  assumption,  however,  is  not  justified  by  facts,  since  we  know,  for  instance, 
that  more  or  less  food  escapes  digestion.  Moreover,  the  calorimetrical  values, 
at  hast  for  proteids,  are  probably  too  high.  In  practice,  therefore,  it  is  nec- 
essary to  ascertain  from  the  excreta  of  the  animal  (see  section  on  Nutrition) 
just  how  much  of  the  ingested  food  has  been  absorbed  and  completely 
or  partially  destroyed  in  the  body. 

Calorimetric  investigations  also  afford  us  indirect  information  as  to  the 
income  of  heat  by  showing  the  quantities  of  heat  produced  and  dissipated. 
Such  data  are  of  much  value,  since  it  is  evident  that  should  the  energy  of  the 
body  be  maintained  in  a  condition  of  equilibrium  from  day  to  day,  and  should 
the  energy  resulting  from  the  transformation  of  potential  energy  be  manifested 
solely  in  the  form  of  heat,  it  follows  that  the  mean  daily  heat-production  and 
income  of  available  energy  must  balance.  But  it  cannot  be  considered  that  this 
balance  is  maintained  at  a  constant  standard  from  hour  to  hour,  nor  from  day 
to  day;  on  the  contrary,  the  fluctuations  are  undoubtedly  considerable,  as  is 
obvious  by  the  fact  that  we  are  continually  expending  energy  and  only  periodi- 
cally (at  meal-time-)  acquiring  energy.  During  fasting  there  is  absolutely  no 
income  of  energy,  yet  the  output  of  heat  may  be  subnormal,  normal,  or  hyper- 
normal  ;  on  the  other  hand,  if  an  exec—  of  energy  be  ingested,  as  in  excessive 
eating,  it  is  not  by  any  means  implied  that  there  is  a  similar  excess  in  heat-pro- 
duetion,  because  >oine  of  the  food  ingested  may  be  lost  as  undigested  food  or  as 
partially  oxidized  excrementitious  matters,  or  may  be  stored  in  the  body  in  the 
form  of  carbohydrate,  fat,  or  proteid;  nor  does  an  excess  of  heat-production 
imply  an  excess  of  income  of  energy,  because  the  stored-up  energy  may  be 
drawn  upon.  (  For  results  of  the  calorimetric  method  see  p.  482.)  The  results 
of  the  various  methods  are  in  close  accord,  and  indicate  that  in  the  adult  the 
total  income  of  available  energy  i>  about  2,500,000  calories. 

Expenditure  of  Heat. — Assuming  that  the  energy  of  the  organism  is 
expended  in  the  form  of  heat,  and  that  the  total  income  of  available  energy  is 
2,500,000  calories,  it  has  been  estimated  by  Yierordt  that  about — 


A NI3IA L   HE. IT.  177 

1.8  per  cent,  is  lost  in  the  urine  and  feces 47,500  calories. 

3.5         "  "  "      expired  air 84,500 

7.2        "  ■"  "      -evaporation  of  water  from  the  lungs     182,120        " 

14.5         "  "  "  "  "  "         skin.     364,120 

73.0        "  "  "       radiation  and  conduction  from  skiu  1, Till, 820        " 

2,500,000  calories. 

Therefore,  about  87.5  per  cent,  is  lost  by  the  skin,  10.7  per  cent,  by  the  lungs, 
and  1.8  per  cent,  in  the  urine  and  feces. 

O.  Heat-production  and  Heat-dissipation. 

Calorimetry. — The  intensity  of  heat  of  any  substance  is  measured  by  means 
of  a  thermometer  or  thermopile ;  the  quantity  of  heat  present  is  estimated  by 
the  weight,  the  specific  heat,  and  the  mean  temperature  of  the  body  ;  the  quan- 
tity of  heat  dissipated  is  measured  by  the  calorimeter ;  and  the  quantity  of 
heat  produced  is  determined  by  the  quantity  dissipated  plus  any  addition  of 
heat  to  that  of  the  body  or  minus  any  that  is  lost  (p.  481).  The  calorie,  or  heat 
unit,  is  the  quantity  of  heat  that  is  necessary  to  raise  the  temperature  of  one 
gram  of  water  1°  C. ;  the  mechanical  unit,  or  grammeter,  is  the  quantity  of 
energy  required  to  raise  one  gram  a  height  of  one  meter,  424.5  grammeters 
being  equal  to  1  calorie;  a  kilocalorie  or  kilogramdegree  is  equal  to  1000 
calories,  and  a  kilogram meter  to  1000  grammeters.  By  specific  heat  is  meant 
the  quantity  of  heat  required  to  raise  the  temperature  of  any  substance  1°  C, 
this  quantity  varying  considerably  for  different  substances.  It"  water  be 
taken  as  1,  as  a  standard  of  comparison,  the  specific  heat  of  the  animal  body 
may  be  regarded  as  being  about  0.8  ;  in  other  words,  0.8  of  the  quantity  of 
heat  will  be  required  to  heat  the  animal  body  as  to  heat  the  same  weight  of 
water.  Knowing  the  weight,  specific  heat,  and  temperature  of  any  substance 
the  total  quantity  of  heat  stored  in  it  at  a  given  temperature,  compared  with 
the  same  body  at  0°  C.  may  be  readily  calculated.  Thus,  if  the  animal 
experimented  upon  weigh  20  kilos,  its  specific  heat  be  0.8,  and  its  temperature 
be  39°,  the  total  quantity  of  heat  stored  would  be  20  X  0.8  X  39°  =  62.4  kilo- 
gramdegrees.  In  calorimetric  work  the  total  heat  in  the  organism  is  seldom 
considered,  but  the  specific  heat  of  the  organism  is  of  importance  in  determin- 
ing the  quantity  of  heat  involved  in  a  change  of  the  animal's  temperature.  For 
instance,  should  the  animal  weigh  20  kilograms  and  its  temperature  be  increased 
or  decreased  0.2°,  the  quantity  of  heat  added  to  or  taken  from  the  heat  of  the 
body,  as  the  case  may  be,  would  be  20X0.8X0.2=3.20  kilograradegrees. 
These  calculations  are  of  fundamental  importance  in  studying  heat-production 
and  heat-dissipation. 

In  making  estimates  of  the  dissipation  of  heat  no  regard  is  paid  usually  to 
the  quantity  lost  in  the  urine  and  feces,  because  the  error  involved  is  so  slight, 
but  the  quantities  imparted  to  the  air,  both  in  wanning  the  inspired  air  and  in 
evaporating  water  from  the  lungs  and  skin,  represent  important  percentages. 

Calorimetry  is  spoken  of  as  direct  and  indirect.  The  former  method  is 
the  direct  determination  of  the  amount  of  heat  produced  and  dissipated  ;  the 


178  AN   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

latter  is  the  indirect  determination  based  upon  estimates  of  the  quantities  of  O 
absorbed  and  COa  eliminated,  or  upon  the  amount  of  potential  energy  ingested 
in  the  food  and  probably  transformed  into  kinetie  energy  within  the  body 
(p.  474). 

Calorimeters  of  various  forms  have  been  employed,  some  of  which  have 
been  devised  to  study  the  body  as  a  whole,  while  others  are  adapted  only  for 
studying  parts,  such  as  a  leu  or  arm.  They  may  be  classified  as  ice,  air,  and 
wafer  calorimeters  in  accordance  with  the  chief  medium  employed  to  absorb 
the  heat.  They  consisl  essentially  of  an  insulated  jacket  of  ice,  air,  or  water, 
which  encloses  the  animal  and  serves  to  absorb  the  heat.  The  ice  calorimeter 
is  impracticable  for  physiological  uses  ;  the  air  calorimeter  until  very  recent 
years  lias  found  but  little  acceptance,  hut  is  deservedly  fast  gaining  in  popular- 
ity; the  water  calorimeter  is  the  form  of  apparatus  usually  employed,  having  been 
first  used  by  Crawford  in  1788;  it  has  been  materially  modified  by  Despretz 
and  Dulong  and  subsequent  investigators.  The  now  classical  instrument  of 
Dulong  consists  of  two  concentric  cases.  The  animal  is  placed  within  the 
smaller  case,  which  is  submerged  in  the  water  contained  in  the  larger  ease, 
this  in  turn  being  placed  within  a  large  box,  between  which  and  the  calorime- 
ter some  non-conducting  material  such  as  feathers  or  wrool  is  packed.  Suit- 
able openings  are  made  for  the  proper  supply  of  fresh  air  and  for  the  agitation 
of  the  water  in  the  calorimeter  so  that  an  equalization  of  the  temperature  of 
the  instrument  can  be  obtained.  This  apparatus  has  certain  serious  defects, 
however,  which  render  it  troublesome  for  expeditious  and  accurate  work.  An 
improved  form  devised  by  the  author1  which  is  now  in  general  use  meets 
every  essential  re(|nircment  for  a  satisfactory  instrument.  The  apparatus  con- 
sists of  two  concentric  boxes  of  sheet  metal  which  are  fastened  together  so  that 
there  is  space  of  about  oue  and  a  half  inches  between  them  filled  with  water 
( Fig.  80).  The  outer  box  is  fifteen  inches  in  height  and  width,  and  eighteen 
inches  in  length.  An  opening  (A)  nine  inches  in  diameter  is  made  in  one  end 
for  the  entrance  and  exit  of  the  animal.  It  is  also  perforated  with  three  small 
holes  in  the  top  corners,  and  a  slit-like  opening  in  the  top  on  one  side.  Two  of 
the  holes  are  for  the  tube-  for  the  entrance  and  exit  of  air  (AW,  EX),  the  entrance 
tube  being  carried  close  to  the  bottom,  while  the  exit  tube  extends  only  to 
the  top  of  the  box,  and  is  placed  in  the  opposite  diagonal  corner,  thus  ensuring 
adequate  ventilation.  In  the  third  hole  a  thermometer  (C  T)  is  inserted, 
by  means  of  which  the  temperature  of  the  calorimeter  (jacket  of  metal  and 
water)  is  obtained.  The  opening  in  the  side  is  for  the  insertion  of  a  stirrer  (S), 
which  is  for  the  purpose  of  thoroughly  mixing  the  water  and  thus  equalizing 
tin'  temperature  of  both  water  and  metal — in  other  words,  of  the  calorimeter. 

Before  using  the  apparatus  the  cahHmetric  equivalent  must  be  determined, 
that  is,  the  amouutof  heat  required  to  raise  the  temperature  of  the  instrument  1°. 
This  may  be  obtained  indirectly  by  knowing  the-  different  substances  used  in 
the  construction  of  the  instrument,  their  weights,  and  their  specific  heats,  and 
estimating  from  these  data.  It  is  better,  however,  to  make  the  determination 
1  Reichert:    University  Medical  Magazine,    L890,  vol.  2,  p.  173. 


ANIMAL   111-: A  '/'. 


479 


by  burning  a  definite  amount  of  absolute  alcohol  or  hydrogen  within  the  instru- 
ment, or  by  using  a  sealed  vessel  of  hot  water  of  a  known  temperature  and 
allowing  it  to  cool  to  a  definite  extent.  The  process  is  simple;  for  instance, 
each  gram  of  alcohol  or  each  liter  of  hydrogen  completely  oxidized  yields  a 
definite  number  of  calories  ;  similarly,  a   definite    weight    of  water  cooled  a 


Fig.  80.— Reichert's  water  calorimeter. 


definite  number  of  degrees  gives  oft'  a  definite  quantity  of  heat.  The  heat  thus 
generated  by  the  oxidation  of  the  alcohol  or  hydrogen  or  given  off  by  the  cool- 
ing of  the  water  is  imparted  to  the  calorimeter  and  increases  its  temperature. 
Knowing  the  quantity  of  heat  given  to  the  calorimeter  and  the  increase  of 
temperature  of  the  instrument,  the  determination  of  the  calorimetrical  equiva- 
lent may  be  easily  made.  Thus,  1  gram  of  alcohol  yields  in  round  numbers 
7000  calories;  if  we  burn  10  grams  of  absolute  alcohol,  70,000  calorics  will 
result;  if  the  temperature  of  the  calorimeter  be  increased  1°,  the  calorimetric 
equivalent  will  be  70,000  calories  or  70  kilogramdegrees ;  in  other  word-,  for 
each  degree  of  increase  of  the  temperature  of  the  calorimeter  a  quantity  of 
heat  equivalent  to  70  kilogramdegrees  is  absorbed. 

The  heat  dissipated  by  an  animal  is  only  in  part  absorbed  by  the  calori- 
meter, another  portion  being  given  to  the  air  which  passes  from  the  instrument, 
and  another  portion  to  water  which  is  evaporated  from  the  lungs  and  skin. 
Three  estimates,  therefore,  arc  necessary — (1)  of  the  heat  given  to  the  calori- 
meter, (2)  of  the  heat  given  to  the  air,  and  (3)  of  the  heat  given  off  in  the 
evaporation  of  water. 

The  estimate  of  the  heat  given  to  the  air  necessitates  the  measurement  of 
the  quantity  of  air  supplied  to  the  calorimeter,  and  of  the  temperature  of  the 


480  AN   AMERICAN    TEXT-HOOK    OF  PHYSIOLOGY. 

air  on  entering  and  leaving  the  calorimeter;  while  the  estimate  of  the  heat  lost 
in  evaporating  water  involves  the  measurement  of  samples  of  the  air  entering 
and  leaving  the  instrument  and  of  the  quantities  of  water  in  both  eases,  the 
total  quantity  of  water  evaporated  from  the  animal  being  estimated  from  these 
data. 

The  conduct  of  such  experiments  is  not  attended  with  any  material  dif- 
ficulties. The  water  of  the  calorimeter  is  stirred  for  a  suffieient  length  of 
time  in  order  to  obtain  a  uniform  temperature.  The  temperature  of  the 
animal  is  taken  and  the  animal  then  placed  within  the  animal  chamber.  The 
temperatures  of  the  calorimeter  and  of  the  air  entering  and  leaving  the  instru- 
ment, and  readings  of  the  three  gas-meters  are  recorded.  During  the  progress 
of  the  experiment  air  temperatures  are  recorded  at  regular  intervals  of  ten  or 
fifteen  minutes  and  the  water  stirred  for  a  few  seconds  each  time.  At  the 
conclusion  of  the  experiment  there  are  recorded — the  temperature  of  the  calori- 
meter, the  temperatures  of  the  air  entering  and  leaving  the  calorimeter,  the 
quantities  of  air  passing  through  the  three  gas-meters,  and  the  temperature  of 
the  animal. 

The  quantity  of  heat  given  to  the  calorimeter  \>  now  determined  by  multi- 
plying the  increase  of  temperature  of  the  instrument  by  the  calorimetric 
equivalent.  If  the  rise  of  temperature  be  0.6°  C.  and  the  calorimetric  equiva- 
lent be  90  kilogramdegrees,  the  quantity  of  heat  imparted  to  the  water  jacket 
will  be  90  X  0.6°  =  54  kilogramdegrees. 

The  quantity  of  heat  imparted  to  the  air  is  determined  by  finding  first  the 
corrected  volume  of  the  air,  then  reducing  the  corrected  volume  to  weight, 
then  multiplying  the  weight  by  the  specific  heat  of  air  at  0°  C,  and  finally 
multiplying  by  the  increase  of  temperature.     The  corrected  volume  may  be 

V      P 

obtained  by  the  following   formula:  V= — ,  where  V  is 

760  (1  +  0.003665  t) 
the  required  volume  at  0°  C.  and  760  mm.  barometric  pressure,  V  the  ob- 
served volume,  P  the  observed  pressure,  and  t  the  observed  mean  temperature: 
760  (1  +  0.00366-0  is  conveniently  obtained  from  standard  tables.  The  errors 
incident  to  changes  in  barometric  pressure  and  in  aqueous  tension  are  so  slight 
that  they  are  not  usually  taken  into  consideration.  Assuming  that  the  quan- 
tity of  air  supplied  amounted  to  6000  liters,  and  that  the  mean  temperature 
of  the   air   was   20°,  the    corrected   volume    would    be,  omitting  barometric 

V  6000 

pre— nre  and  aqueous  tension,  V  =  —  —  =  5590  liters 

(1  +  0.0036656  t)  1,0733 
at  0°  C.  One  liter  of  dry  air  at  0°  C.  weighs  0.001293  kilogram  ;  therefore, 
559*  I  liters  x  0.001293  =  7.22s  kilograms.  1 1'  we  assume  that  the  air  during 
its  passage  through  the  calorimeter  had  its  temperature  increased  3°,  and  the 
specific  heat  of  air  is  O.L>:',77.  the  quantity  of  heat  imparted  to  the  air  must 
have  been  7.228  x  3  x  0.2377  =  5.152  kilogramdegrees. 

The  next  estimate  is  of  the  quantity  of  heat  lost  in  the  evaporation  of 
water.     This  is  determined   by  finding  the  difference  between  the  quantities 


ANIMAL   HEAT.  481 

of  water  in  the  samples  of  the  air  passiug  into  and  from  the  calorimeter,  and 
estimating  from  these  results  the  amount  of  moisture  imparted  to  the  total  air 
leaving  the  chamber.  Assuming  that  10  grams  of  water  were  thus  evaporated, 
since  each  gram  requires  about  582  calories  or  0.582  kilogramdegree,  the  quan- 
tity of  heat  evolved  would  be  equal  to  10  X  0.582  =  5.82  kilogramdegrees. 

The  total  quantity  of  heat  dissipated  would  therefore  be  the  sum  of  the 
quantities  given  to  the  calorimeter,  to  the  air,  and  to  the  water  evaporated : 

Given  to  the  calorimeter 54,001)  kilogramdegrees. 

Given  to  the  air 5,152  " 

Lost  in  evaporating  water 5,820 

Total  heat-dissipation ti4/J72  " 

The  quantify  of  heat  produced  is  determined  by  adding  to  or  subtracting 
from  the  quantity  dissipated  the  amount  of  heat  that  may  have  been  gained 
or  lust  by  the  organism.  It  is  obvious  that  any  difference  between  the 
quantities  of  heat  dissipated  and  produced  must  be  represented  by  an  increase 
or  decrease  of  the  mean  temperature  of  the  animal.  If  the  animal's  tempera- 
ture remains  unchanged,  the  quantity  of  heat  produced  is  the  same  as  the 
quantity  lost;  if,  however,  the  animal's  temperature  increases,  less  heat  is 
dissipated  than  is  produced  ;  if  it  falls,  vice  versa.  The  quantity  of  heat 
involved  in  a  change  of  body-temperature  is  determined  by  the  product  of 
the  change  in  temperature  into  the  animal's  weight  and  specific  heat.  Assum- 
ing that  the  animal's  temperature  at  the  beginning  of  the  experiment  was 
38.95°  C.  and  at  the  end  39.32°  C,  the  temperature  being  increased  0.37°  C, 
that  the  animal's  weight  was  25  kilograms,  and  that  the  animal's  specific  heat 
was  0.8,  the  quantity  of  heat  would  be  0.37  X  25  X  0.8  =  7.4  kilogramdegrees. 
The  quantity  of  heat  produced  would,  therefore,  be  the  total  quantity  dissipated 
plus  the  quantity  of  heat  added  to  the  heat  of  the  organism  at  the  time  the 
experiment  begun  ;  therefore,  the  heat-production  was  64.972  -\-  7.4  =  72.372 
kilogramdegrees.  If  the  animal's  temperature  had  fallen,  more  heat  would 
have  been  dissipated  than  produced,  because  the  total  quantity  of  heal  in  the 
organism  was  greater  at  the  beginning  than  at  the  end  of  the  experiment  ; 
therefore,  the  quantity  of  heat  represented  in  the  change  of  temperature  would 
have  been  deducted  from  the  quantity  of  heat  dissipated. 

While  calorimetric  experiments  do  not  generally  involve  any  special  diffi- 
culties, accurate  results  can  only  be  ensured  by  the  strict  observation  of  certain 
details:  (1)  The  temperatures  of  the  calorimeter  and  room  should  be  as  nearly 
as  possible  alike  and  kept  as  far  as  possible  constant.  (2)  The  thermometers 
employed  should  be  SO  sensitive  that  readings  can  be  made  in  hundredths  of  a 
degree,  and  they  should  respond  very  quickly,  SO  that  rectal  temperatures  can 
be  obtained  within  three  minutes.  (3)  Rectal  temperatures  are  to  be  preferred, 
the  thermometer  always  being  inserted  to  the  same  extent  and  held  in  the 
same  position,  care  being  exercised  to  prevent  the  burying  of  I  he  bulb  in  fecal 
matter.  (4)  The  animal  during  the  taking  of  its  temperature  must  on  no 
account  be  tied  down,  but  gently  held,  and  all  circumstances  seduously  avoided 
Vol.  r.— 31 


182 


i.v    AMERICAN    TEXT-BOOK    OF   PlfYSIOLOd  V. 


that  tend  to  excite  the  animal.  Tin-  chief  sources  of  error  in  the  calorime- 
try  are  in  failures  to  obtain  accurate  temperatures  of  the  calorimeter  and  of 
the  animal.  In  the  latterea.se  inaccuracy  is  to  some  extent  absolutely  una- 
voidable, chiefly  because  of  normal  fluctuations  which  occur  frequently  and  are 
often  very  marked. 

Conditions  affecting-  Heat -production. — The  quantity  of  heat  produced 
must  necessarily  vary  with  many  circumstances.  Estimates  of  heat-production 
in  the  adult  range  in  round  numbers  from  2000  to  3000  kilogramdegrees  per 
diem  according  to  the  method  and  incidental  circumstances.  Thus,  according 
to— 


vScliarling 3169  kilogramdegrees 

Vogel 2400  " 

Him      3725  " 

Leyden 2160  " 

Hemholtz 2732  " 

Rosenthal 2446  " 

Danilesky 3210  « 

Ludwig 3192  " 


Ranke 2272  kilogramdegrees 

Kiibner 2843  " 

Ott 103  '• 

per  hour  during  the  afternoon   (weight  of 

man  87.3  kilograms). 
Lichatschew   ....    33.072  to  38.723  kilo- 

gramdegrees  per  kilogram   of  body-weigh! 

per  diem.1 


The  chief  conditions  which  affect  heat-production  are  age,  sex,  constitution, 
body-weight  and  body  surface,  species,  respiratory  activity,  the  condition  of 
the  circulation,  internal  and  external  temperature,  food,  digestion,  time  of  day, 
muscular  activity,  the  activity  of  heat-dissipation,  nervous  influences,  drugs, 
abnormal  and  pathological  conditions. 

Young  animals  produce  more  heat,  weight  for  weight,  than  the  mature.  This 
is  owing  chiefly  to  the  greater  activity  of  the  metabolic  processes  in  the  former, 
and  in  part  to  the  relatively  larger  body  surface,  young  animals  generally 
being  smaller  than  the  matured  and  thus  having,  in  proportion  to  body-weight, 
larger  radiating  surfaces. 

Heat-production  is  more  active  in  the  robust  than  in  the  weak,  other  con- 
ditions being  the  same. 

The  weight  of  the  body  is  obviously  a  most  important  factor  in  relation  to 
the  quantity  of  heat  produced,  especially  as  regards  the  weight  of  the  active 
tissues  in  relation  to  inactive  structures  such  as  bone,  sinew,  and  cartilage. 
Two  animals  of  the  same  weight  may  produce  very  different  quantities  of 
heat  per  diem,  other  things  being  equal.  Thus,  a  fleshy  animal  should 
naturally  be  expected  to  produce  more  heat  than  one  with  very  little  flesh  and 
an  abundance  of  fat,  which  is  an  inactive  heat-producing  structure.  While, 
therefore,  the  relation  of  heat-production  to  body-weight  does  not  seem  to  be 
definite,  yet  the  experiments  by  Reichert 2  and  by  Carter 3  indicate  that  heat- 
production  bears,  broadly  speaking,  a  direct  relation  to  body-weight. 

Heat-production  is  greater  relatively  in  homothermous  than  in  poikibther- 

1  The  figures  by  ott   {New  York   Medical  Journal,  1889,  vol.   16,   p.  29)  and   Lichatschew 

inauguralis,  St.  Petersburg,   1893;   quoted   in   Hermann's  Jahresberichte  der  Physioloyie, 
3.  99)  were  obtained  by  means  of  a  water  calorimeter. 

2  University  Medical  Magazine,  1890,  vol.  '_',  p.  225. 

3  Journal  of  Nervous  and  Mental  Diseases,  1890,  v>>\.  17,  p.  782. 


ANIMAL   HEAT. 


483 


mous  animals;  it  varies  materially  in  intensity  in  different  species,  especially  in 
warm-blooded  animals;  and  it  is  closely  related  to  the  intensity  of  respiration. 
Moreover,  it  is  probable  that  each  species,  and  even  each  individual  of  the 
species,  has  its  own  specific  thermogenic  coefficient,  that  is,  a  mean  standard  of 
heat-production  for  each  kilogram  of  body-weight  or  for  each  square  centime- 
ter of  body-surface.  The  following  figures  giving  the  heat-production  per 
kilogram  per  hour,  compiled  by  Munk,1  are  of  interest  both  as  regards  species 
and  size  and  weight  of  the  animal  in  relation  to  heat-production  : 


Horse 1.3  kilogramdegrees. 

Man 1.5  " 

Child  (7  kilograms)  .    .  3.2  " 

Dog  (30  "       )  .    .  1.7  " 

Dog     (3  "       )  .    .  3.8  " 

Guinea-pig 7.5  " 


Duck 6.0  kilogramdegrees. 

Pigeon 10.1  " 

Rat 11.3  " 

Mouse 19.0  " 

Sparrow 35.5  " 

Greenfinch 35.7  " 


These  figures  have  an  additional  interest  when  compared  with  the  respira- 
tory activity  of  different  species  (p.  429).  The  intensity  of  respiration  has  a 
marked  significance  both  in  connection  with  the  species  and  the  individual. 
The  larger  the  quantity  of  oxygen  consumed  the  greater  relatively  is  the 
activity  of  oxidation  processes,  and,  consequently,  the  more  active  is  heat-pro- 
duction (see  p.  429).  Therefore,  all  circumstances  which  affect  respiratory 
activity  tend  to  affect  thermogenesis.  The  intensity  of  respiratory  activity  and 
the  extent  of  body-surface  in  relation  to  body-weight  are  closelv  related  (p. 
430). 

Increased  activity  of  the  circulation  is  favorable  to  increased  heat-produc- 
tion, this  being  due  to  several  factors:  (1)  A  more  abundant  supply  of  blood 
may  be  accompanied  by  increased  metabolic  activity.  (2)  Increased  circulatory 
activity  is  favorable  to  increased  heat-dissipation  by  causing  a  larger  supply 
of  blood  to  the  skin,  thus  facilitating  loss  by  radiation  and  indirectly  tending  to 
increase  thermogenesis.  (3)  Increased  circulatory  activity  also  excites  the  respi- 
ratory movements  and  the  secretion  of  sweat,  thus  increasing  heat-loss  and  in- 
directly favoring  heat-production.  (4)  The  more  active  the  circulation  the 
larger  the  amount  of  heat  produced  by  the  heart  and  the  movement  of  the 
blood.  The  diurnal  fluctuations  of  the  pulse-rate  are  said  to  be  more  or  less 
closely  related  to  similar  changes  of  body  temperature. 

Arise  of  internal  temperature  (body  temperature)  is  favorable  to  increased 
metabolic  activity  (p.  432)  and,  therefore,  to  an  increase  of  heat-production  ; 
conversely,  a  fall  of  body  temperature  tends  to  reduce  heat-production.  The 
influences  of  body  temperature  are,  as  a  whole,  less  important  than  those  of 
external  temperature. 

The  influences  of  external  temperature  axe  in  a  measure  differenl  upon  homo- 

thermous  and  poikilothermous  animals.     In  the  former,  heat-production  is  in 

inverse  relation  to  the  temperature  of  the  surrounding  medium,  so  that  the 

cooler  the  ambient  temperature  the  greater  the  heat-production  ;  in  the  latter 

1  Physiologie  dea  Menachen  und  der  Sdugethiere,  L892,  8.  302. 


1M  AN   AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

heat-production  increases  with  an  increase  of  external  temperature,  because 
with  the  rise  of  the  latter  bodily  temperature  increases,  which  in  turn  increases 
metabolic  activity  (pp.  4:52,  433).  ( lonsequently,  in  warm-blooded  animals  heat- 
production  is  greater  in  cold  climates  and  seasons  than  in  the  opposite  conditions, 
while  in  cold-blooded  animals  the  opposite  is  the  case.  Cold  applied  to  the  skin 
increases  heat-production  by  reflex ly  exciting  muscular  activity  (shivering,  etc., 
p.  433) ;  moderate  heat  exerts  the  opposite  influence  unless  the  bodily  tem- 
perature is  affected,  as  shown  by  the  results  of  studies  of  respiration  (p.  433). 

The  character  of  the  food  is  important.    Danilewsky1  has  estimated  that  the 
following  quantities  of  heat  are  produced  under  different  diets,  etc.  : 

On  a  minimum  diet 1800  kilogramdegrees. 

On  a  reduced  diet  (absolute  rest) 1989 

On  a  non-nitrogenous  diet 2480  " 

On  a  mixed  diet  (moderate  work) 3210  " 

On  an  abundant  diet  (hard  work) 3646  " 

On  an  abundant  diet  (very  laborious  work) 3780 

The  influence  of  the  quantity  and  quality  of  the  diet  must  be  potent  when 
it  is  remembered  that  1  gram  of  proteid  yields  about  4100  calories,  1  gram  of 
fat  about  9312  calories,  and  1  gram  of  carbohydrate  about  4116  calories.  In 
cold  climates  fats  enter  very  largely  into  the  diet  because  of  the  greater  loss 
of  heat  and  the  consequent  increased  demand  for  heat-producing  substances. 

During  the  periods  of  digestion  more  heat  is  produced  than  during  the  in- 
tervals, this  increase  being  due  chiefly  to  the  muscular  activity  of  the  intestinal 
walls  (p.  431).  Langlois'  experiments  indicate  that  during  digestion  heat- 
production  may  be  increased  35  to  45  per  cent. 

It  is  said  that  heat-production  undergoes  diurnal  variations  which  corre- 
spond with  the  fluctuations  of  bodily  temperature,  but  this  is  doubtful. 

All  structures  produce  more  heat  during  activity  than  during  rest.  Heat- 
production  has  been  estimated  to  be  from  two  and  a  half  to  three  times  greater 
when  awake  and  resting  than  when  asleep,  and  from  one  and  a  half  to  three 
times  more  when  active  than  when  at  rest,  in  proportion  to  the  degree  of 
activity.  During  hybernation  the  absorption  of  O  falls  considerably  (p.  434), 
consequently  heat-production  is  believed  to  decline  to  a  like  degree. 

All  conditions  which  affect  heat-dissipation  (p.  494)  tend  indirectly  to 
influence  heat-production. 

The  most  important  of  the  factors  influencing  heat-production  is  the  ner- 
vous mechanism  which  controls  the  heat-producing  processes  (p.  490). 

Various  dnu/s  exert  more  or  less  potent  influences  directly  or  indirectly  upon 
heat-production.  Cocain,  strychnin,  brucin,  and  other  motor  excitants  increase 
heat-production;  while  chloroform,  most  antipyretics,  narcotics  generally,  bro- 
mides, and  motor  depressants  decrease  heat-production. 

I  bat-production  is  diminished  in  most  forms  of  anaemia,  after  severe  hem- 
orrhage, and  in  most  non-febrile  adynamic  conditions.  It  is  usually  increased 
in  fevers,  especially  so  in  infectious  fevers.  According  to  Liebermeister,  the 
1  Pflugei>s  Arehivfur  Physiologk,  1883,  Bd.  xxx.  S.  190. 


ANIMAL    HEAT.  485 

increase  in  fever  is  probably  about  6  per  cent,  for  each  increase  of  1°  C.  of 
bodily  temperature,  so  that  were  the  increase  of  temperature  3°  C.  the  increase 
of  heat-production  would  be  18  per  cent. 

Conditions  affecting-  Heat-dissipation. — The  loss  of  heat  from  the  body 
occurs  through  several  channels — in  the  urine,  feces,  sweat,  and  expired  air, 
and  by  radiation  and  conduction  from  the  skin;  hence,  all  conditions  which 
affect  the  loss  of  heat  in  the  above  ways  must  influence  heat-dissipation.  The 
chief  of  these  are :  Age,  sex,  species,  the  quantity  of  subcutaneous  fat,  the 
nature  of  the  surrounding  medium,  clothing,  internal  and  external  tempera- 
ture, activity  of  heat-production,  body-surface,  the  condition  of  the  circulation, 
respiration,  sweat,  activity,  radiating  coefficient,  nervous  influences,  drugs,  and 
abnormal  conditions. 

The  influence  of  age  is  shown  by  the  fact  that  the  young  dissipate  and 
produce  more  heat  in  proportion  to  body-weight  than  the  adult,  this  being  due 
chiefly  to  the  relatively  greater  metabolic  activity  and  the  larger  proportional 
body-surface  (p.  430),  and  consequent  greater  radiation,  in  the  young. 

Sex  per  se  does  not  seem  to  exert  any  influence,  although  the  adult  human 
female,  weight  for  weight  and  for  an  equivalent  bodily  surface,  probably  dissi- 
pates less  heat  than  the  male,  because  of  her  relative  abundance  of  subcu- 
taneous fat,  which  hinders  heat-dissipation.  No  difference  so  far  as  sex  is 
concerned  has  been  noted  in  the  lower  animals. 

Heat-dissipation  varies  greatly  in  different  sjiecies,  owing  chiefly  to  relative 
size  and  respiratory  activity,  to  the  nature  of  the  medium  in  which  the  animal 
lives,  and  to  the  character  of  the  body-covering.  Heat-dissipation  is  more 
active  in  homothermous  animals  than  in  poikilothermous  animals,  because  of 
the  greater  activity  in  the  former  of  heat-production.  In  amphibia  heat-dissi- 
pation is  greater  when  the  animal  is  in  the  water  than  when  exposed  to  the  air 
if  both  water  and  air  be  of  the  same  temperature,  because  water  is  a  better 
conductor  of  heat  and  consequently  withdraws  heat  from  the  body  more 
rapidly.  The  higher  the  temperature  of  the  surroundings  the  higher  the 
bodily  temperature  of  cold-blooded  animals,  consequently  the  greater  are  heat- 
production  and  heat-dissipation.  In  warm-blooded  animals  the  effect  on  both 
heat-production  and  heat-dissipation  is  in  inverse  relation  to  the  surrounding 
temperature  (unless  the  bodily  temperature  is  affected),  external  heat  decreasing 
both  heat-dissipation  and  heat-production,  and  internal  heat  increasing  both. 

Subcutaneous  fat  is  a  poor  conductor  of  heat,  consequently  the  greater  the 
abundance  of  it  the  greater  the  hindrance  offered  to  the  dissipation  of  heat. 
The  value  of  fat  in  this  respect  is  illustrated  in  water-fowls,  which,  as  a  rule, 
are  far  more  abundantly  supplied  with  fat  than  other  species;  and  by  the  ex- 
ceptional abundance  of  subcutaneous  fat  in  species  of  fowl  which  inhabit  very 
cold  waters.  Bathing  the  skin  with  grease  hinders  radiation,  and  is  adopted 
by  swimmers  both  to  conserve  the  bodily  heat  and  to  protect  the  skin. 

When  air  and  water  are  of  the  same  temperature,  heat-dissipation  is  greater 
when  the  animal  is  exposed  to  the  water,  because  the  latter  is  abetter  con- 
ductor.     Heat-loss    is  greater   in   dry   than   in    moist    air,   other  things   being 


186  AN   AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

equal,  because  in  the  former  the  evaporation  of  sweat  from  the  body  and  the 
loss  of  \\at<r  from  the  lungs  are  favored,  the  vaporization  of  water  affecting 
heat-dissipation  more  decidedly  than  the  moisture  of  the  air.  Heat-dissipation 
is  more  active  in  cold  moist  air  than  in  cold  dry  air.  Cold  air  is  not  favorable 
to  the  vaporization  of  water,  whereas  cold  moist  air  has  a  higher  specific  heat 
than  the  dry  air,  and  thus  tends  to  carry  oil"  heat  more  rapidly. 

The  character  of  the  covering  of  the  body  is  of  great  importance.  This 
is  illustrated  in  the  changes  which  occur  in  the  natural  covering  of  animals 
during  warm  and  cold  seasons,  and  in  the  characters  of  the  fur  of  species 
which  inhabit  very  cold  or  very  warm  climates.  During  the  winter  the  fur 
is  longer  and  thicker  than  during  the  summer.  Animals  living  in  cold  or  hot 
climates  are  supplied  with  a  relatively  greater  or  less  abundance  of  fur  or 
feathers  and  subcutaneous  fat.  Man  provides  for  changes  of  the  seasons  by 
modifying  the  quantity  and  quality  of  his  clothing.  In  the  adaptation  of 
dress  to  climate,  the  conductivity,  radiating  coefficient,  hygroscopic  capacity, 
porosity,  weight,  and  color  of  the  clothing  are  important  factors.  The  poorest 
conductors,  other  things  being  equal,  make  the  warmest  clothing;  fur  and 
wool  are  poor  conductors  and  therefore  are  adapted  especially  for  cold  seasons 
and  climates,  while  cotton  and  linen  are  good  conductors  and  therefore  make 
cool  clothing.  The  radiating  coefficient  depends  upon  the  conductivity  of  the 
material  and  the  character  of  the  radiating  surface.  The  coarser  the  material 
the  better  the  radiating  surface,  hence  the  better  the  conductor  and  the  cooler 
the  clothing.  The  hygroscopic  character  of  the  clothing  is  of  far  more 
importance  than  is  generally  believed.  Articles  of  clothing  having  a  large 
capacity  for  absorbing  and  retaining  moisture  are,  other  things  being  equal, 
of  more  value,  especially  for  underwear,  than  those  possessing  the  opposite 
quality.  Woollen  goods  compared  with  those  made  of  cotton  not  only  have 
;i  far  greater  absorptive  capacity  but  retain  moisture  for  a  longer  time.  "When 
the  clothing  is  of  wool  people  are  less  apt  to  catch  cold  from  exposure  to 
draughts  and  sudden  cold  than  when  it  is  of  linen  or  cotton,  the  wool  pre- 
venting a  too  rapid  evaporation  of  moisture,  thus  guarding  against  chilling. 
Porosity  is  a  comparatively  subsidiary  factor.  The  greater  the  weight  of  the 
clothing,  other  things  being  equal,  the  more  is  heat-dissipation  hindered.  The 
color  of  the  outer  apparel  has  a  certain  influence  owing  to  the  relative  heat- 
absorbing  capacities,  black  clothing  being  wanner  than  white,  etc.,  hence  the 
genera]  use  of  white  or  light-colored  clothing  in  warm  climates  and  seasons. 

A  rise  of  internal  temperature  (bodily  temperature)  is  favorable  to  an  in- 
crease of  heat-dissipation,  for  several  reasons:  (1)  I  bat-production  tends  to 
be  increased  and  thus  cause  an  effort  of  the  system  to  get  rid  of  the  excess  of 
heat.  (2)  The  activity  of  the  circulation  is  increased,  causing  a  larger  amount 
of  blood  to  be  brought  to  the  cutaneous  surface  where  it  is  subjected  to  the 
influence  of  the  cooler  surroundings.  (3)  Respiratory  movements  are  increased 
so  that  heat-dissipation  is  favored  by  the  larger  amount  of  air  respired  and 
larger  amount  of  moisture  carried  off.  (1)  The  temperature  of  the  body  is 
higher  in    relation   to  that  of  the  surroundings  and    thus  heat-dissipation  by 


ANIMAL   HEAT.  487 

radiation  and  conduction  is  facilitated.  The  influences  of  external  tempera- 
ture are  even  more  potent  in  their  effects  than  those  of  internal  temperature, 
chiefly  because  of  the  much  wider  range  of  temperature  to  which  the  organism 
is  subjected.  Bodily  temperature  under  ordinary  circumstances  does  not  vary- 
more  than  1°  to  2°  C.  during  the  twenty-four  hours,  but  external  temperature 
may  vary  as  much  as  40°  C,  or  more.  External  heat  tends  by  exciting  cuta- 
neous nerves  to  reflexly  diminish  heat-prod  notion  and  thus  indirectly  dimin- 
ish heat-dissipation  ;  but  this  is  to  some  extent  antagonized  by  a  dilatation  of 
the  blood-vessels  of  the  skin,  an  excitation  of  respiration,  and  increase  in  the 
quantity  of  sweat,  all  of  which  tend  to  increase  heat-dissipation,  but  which 
are  unable  to  balance  the  opposite  effects.  Cold,  on  the  other  hand,  accelerates 
both  heat-dissipation  and  heat-production.  The  loss  of  heat  from  the  body 
is  increased  because  of  the  greater  difference  in  the  temperatures  of  the  body 
and  the  surroundings  ;  but,  on  the  other  hand,  the  cutaneous  vessels  are  con- 
tracted, the  circulation  is  less  active,  and  the  quantity  of  sweat  is  lessened,  all 
of  which  are  unfavorable  to  heat-dissipation.  Yet  while  these  latter  altera- 
tions tend  to  diminish  heat-loss,  they  are  not  sufficient  to  compensate  for  the 
increased  expenditure  by  radiation  and  for  the  greater  loss  by  respiration. 

Circumstances  which  increase  heat-production  above  the  normal  tend  indi- 
rectly to  increase  heat-dissipation.  Other  things  being  equal,  the  greater  the 
quantity  of  heat  produced  the  greater  the  heat-dissipation,  unless  the  bodily 
temperature  be  below  the  normal,  in  which  case  heat-production  may  be  in- 
creased and  yet  heat-dissipation  remain  unaffected,  or  even  be  diminished,  until 
sufficient  heat  has  accumulated  to  bring  the  bodily  temperature  up  to  the 
mean   standard. 

The  larger  the  surface  of  the  body  exposed  to  the  normally  cooler  sur- 
roundings, the  greater  is  the  loss  of  heat.  The  larger  the  animal  the  greater  the 
body-surface,  and  therefore  the  greater  is  heat-dissipation  ;  but  in  proportion 
to  body-weight  smaller  animals  have  larger  body-surfaces,  therefore  heat-dissi- 
pation is  relatively  greater,  although  not  absolutely  so  (see  p.  4.°><M.  The  area 
of  body-surface  involved  in  heat-dissipation  is  affected  by  the  position  of  the 
individual.  Thus,  by  bringing  the  arms  and  legs  in  contact  with  the  body 
the  total  surface  exposed  is  lessened.  On  the  other  hand,  animals  which 
habitually  have  their  legs  in  apposition  with  the  trunk  have  their  radiating 
surfaces  increased  when  their  legs  are  extended.  For  instance,  in  the  rabbif 
extension  of  the  legs  enormously  increases  heat-dissipation,  so  that  the  bodily 
temperature  is  profoundly  affected. 

The  condition  of  the  vascular  system  exercises  an  important  influence. 
Circumstances  that  excite  the  circulation  affect  heat-dissipation  both  directly 
and  indirectly.  Thus,  heat-loss  is  directly  increased  by  the  excitatioD  of  the 
respiratory  movements,  by  the  increased  secretion  of  sweat,  and  by  the  larger 
supply  and  increased  temperature  of  the  blood  to  the  skin.  Increased  activity 
of  the  circulation  also  increases  heat-production,  ami  thus  indirectly  affects  heat- 
dissipation.     Opposite  conditions,  of  course,  lessen  heat-dissipation. 

The  larger  the  quantity  of  air  respired,  other  things  being  equal,  the  larger 


488  AN    AMERICAN    TEXT-HOOK    OF   PHYSIOLOGY. 

the  lo>>  of  heat  by  this  channel.  The  heat-loss  occurs  both  in  warming  the 
air  and  in  the  evaporation  of  water  from  the  lungs,  so  that  the  cooler  and 
drier  the  air  inspired  the  larger  relatively  is  the  heat-loss.  The  importance 
of  respiration  as  a  heat-dissipating  factor  is  illustrated  by  the  fact  that  about 
10.7  per  cent,  of  the  total  heat-dissipation  occurs  in  this  way  (see  p.  477). 

Next  in  importance  to  radiation  is  the  amount  of  water  evaporated  from 
the  sldn.  Each  gram  of  water  requires  582  calories  to  vaporize  it,  and  it  is 
estimated  (p.  477)  that  364,120  calories  are  dissipated  in  this  way,  or  14.5 
percent,  of  the  total  heat-dissipation.  An  increase  of  external  temperature 
increases  the  irritability  of  the  sudoriparous  glands,  thus  favoring  secretion  and 
heat-dissipation.  The  value  of  sweat,  however,  as  a  means  of  carrying  off 
heat,  is  materially  affected  by  the  temperature  of  the  air  as  well  as  by  the 
amount  of  moisture  present.  The  higher  the  temperature  and  the  less  the 
moisture  the  more  rapidly  evaporation  occurs,  and  consequently  the  greater 
the  loss  of  heat  ;  when  air  i>  moist  and  of  high  temperature  evaporation  takes 
place  relatively  slowly,  if  at  all.  Therefore,  individuals  can  withstand  sub- 
jection to  dry  air  of  a  higher  temperature  and  for  a  longer  period  than  when 
the  atmosphere  is  moist.  In  the  former  case  sweat  is  rapidly  secreted  and 
vaporized,  and  thus  a  marked  rise  of  internal  temperature  may  be  prevented. 
James  found  that  a  vapor  bath  at  44.5°  C.  (112°  F.)  was  insufferable,  while 
dry  air  at  80°  C.  (176°  F.)  caused  little  inconvenience.  When  air  is  of  high 
temperature  and  loaded  with  moisture  we  say  that  it  is  "sultry,"  but  dry  air 
of  the  same  temperature  is  not  unpleasant. 

Muscular  activity  increases  heat-production,  excites  the  circulation  and 
respiration,  and  increases  the  secretion  of  sweat,  all  of  which  directly  or  indi- 
rect Iv  increase  heat-dissipation. 

The  surface  of  //"  body  as  a  radiating  surface  cannot  be  regarded  in  the 
same  light  as  an  indifferent,  inanimate  surfape,  such  as  metal  or  wood.  The 
coefficient  of  r<i<Iiafi<>n  (the  quantity  of  heat  emitted  during  a  unit  of  time  at  a 
standard  temperature  from  a  given  area)  in  an  inanimate  body  remains  fixed, 
because  the  surface  itself  is  virtually  unchangeable;  but  the  coefficient  for  the 
living  organism  is  subject  to  material  alterations.  These  alterations  depend 
chiefly  (1)  upon  the  actions  of  the  pilo-motor  mechanism  whereby  the  relation 
of  the  natural  covering  (hair  or  feathers  in  the  lower  animals)  of  the  body  to 
the  skin  is  effected  ;  (2)  upon  changes  in  the  conductivity  of  the  skin  owing  to 
variations  of  the  blood-supply  ;  (3)  upon  the  varying  thickness  of  the  skin  in 
different  species,  in  different  individuals,  and  in  different  parts  of  the  body; 
(4)  upon  the  temperature  of  the  surroundings;  (5)  upon  the  extent  of  the 
body-surface  exposed;  Hi)  upon  the  character  of  the  clothing.  When  the 
arrector  pili  muscles  contract  the  skin  is  made  tense  and  the  cutaneous  blood- 
vessels .ire  pressed  upon  and  rendered  anaemic,  thus  lessening  the  quantity  of 
fluid  in  the  skin  and  as  a  consequence  lowering  the  coefficient  of  dissipation; 
moreover,  in  animals  whose  natural  covering  is  fur  or  leathers,  these  fibres 
cause  an  erection  of  one  or  the  other,  a-  the  case  may  be,  and  in  this  way 
affect    the   radiating   coefficient.     The   coefficient    is  enormously  increased  by 


ANIMAL   HEAT.  489 

removing  the  natural  covering,  such  as  the  fur  of  the  rabbit,  under  which  cir- 
cumstances, even  though  the  animal  be  subjected  to  a  relatively  high  external 
temperature,  heat-dissipation  is  so  enormously  increased  that  death  ensues  within 
two  or  three  days.  When  one  side  of  the  body  of  a  horse  was  shaved  and  the 
animal  subjected  to  an  atmosphere  having  a  temperature  of  0°  C,  the  tem- 
perature of  the  skin  of  the  shaven  side  fell  8°  in  forty  minutes,  while  the 
temperature  of  the  unshaven  side  fell  only  0.5°. 

The  coefficient  is  diminished  where  there  is  excessive  sebaceous  secretion, 
and  where  grease  is  artificially  applied,  and  by  an  accumulation  of  subcutaneous 
fat ;  it  is  increased  by  wetting  the  skin,  as  by  sweat  or  bathing ;  and  it  is 
affected  by  many  other  circumstances. 

Through  the  operations  of  the  nervous  system  heat-dissipation  may  be 
affected  directly  or  indirectly  by  action  upon  the  heat-dissipating  and  heat- 
producing  processes — circulation,  respiration,  sudorific  and  sebaceous  glands, 
and  arrector  pili  muscles. 

There  are  many  drugs  which  directly  or  indirectly  affect  heat-dissipation. 
Drugs  which  cause  dilatation  of  the  cutaneous  vessels  tend  to  increase  heat- 
dissipation  ;  conversely,  those  which  cause  contraction  of  the  blood-vessels 
hinder  dissipation.  Diaphoretics  increase  heat-loss  essentially  by  increasing 
the  amount  of  sweat.  Respiratory  excitants  increase  the  loss  of  heat  by  means 
of  the  increased  volume  of  air  respired.  Drugs  which  increase  heat-production 
tend  to  indirectly  increase  heat-dissipation. 

All  pathological  states  which  affect  heat-production  tend  to  similarly  disturb 
heat-dissipation.  Conditions  of  malnutrition  favor  heat-dissipation  by  causing 
a  loss  of  subcutaneous  fat,  but  this  is  to  a  greater  or  less  extent  compensated 
for  by  the  enfeeblement  of  the  circulation,  respiration,  and  metabolic  processes 
in  general.  In  fever,  both  heat-production  and  heat-dissipation  are  generally 
increased,  the  former  being  affected  more  than  the  latter,  so  that  the  bodily 
temperature  rises.  In  some  forms  of  fever  the  rise  of  temperature  is  essentially 
due  to  diminished  heat-dissipation. 

D.  The  Heat-mechanism. 

The  heat-mechanism  consists  of  two  fundamental  parts,  one  being  concerned 
in  heat-production,  and  the  other  in  heat-dissipation.  Heat-production  is 
briefly  expressed  as  thermogenesis ;  and  heat-dissipation,  as  thermolysis.  The 
operations  of  these  mechanisms  are  so  intimately  related  that  fluctuations  in  the 
activity  of  one  are  rapidly  compensated  for  by  reciprocal  changes  in  the  other, 
so  that  under  normal  conditions  heat-production  and  heat-dissipation  so  nearly 
balance  that  the  mean  bodily  temperature  is  maintained  within  narrow  limits. 

The  regulation  of  the  relations  between  heat-production  and  heat-dissipation 
is  termed  thermotaxis,  which  regulation  may  be  effected  by  alterations  in  either 
thermogenesis  or  thermolysis. 

The  Mechanism  concerned  in  Thermogenesis. — The  portion  of  the  heat- 
mechanism  concerned  in  heat-production  consists  of  (1)  thermogenic  tissues, 
(2)  thermogenic  nerves,  and  (3)  thermogenic  centres. 


490  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

The  Thermogenic  Tissues. — Almost  if  not  every  tissue  of  the  body  may  be 
regarded  as  being  a  heat-producing  structure.  The  very  tact  that  oxidative 
processes  lie  at  the  bottom  of  all  forms  of  vital  activity,  and  that  heat-produc- 
tion is  a  concomitant  of  oxidation,  leads  inevitably  to  the  conclusion  that  as 
Ion-  as  cells  possess  life  they  must  produce  heat.  There  arc,  however,  certain 
of  the  bodily  structures,  especially  the  skeletal  muscles  and  the  gland-,  which 
are  exceptionally  active  as  heat-producers.  Indeed,  in  the  case  of  the  skeletal 
muscles  the  heat-producing  processes  are  of  such  a  character  as  to  justify  the 
belief'  that  with  them  therniogendsis  is  a  specific  function,  because  heat  is  pro- 
duced not  merely  as  an  incidental  product  of  activity  but  as  a  specific  product. 
When  a  muscle  contracts,  heat  is  evolved  as  an  incident  of  the  performance  of 
work,  and  when  it  is  at  rest  heat  is  produced  not  only  as  an  incident  of  growth 
and  repair  but  as  the  result  of  a  specific  act.  This  latter  is  proved  by  the  fact 
that  when  the  muscles  have  been  in  a  state  of  prolonged  rest,  when  the  chemi- 
cal changes  concerned  in  growth  and  in  repair  of  waste  are  practically  inactive, 
heat-production  continues  to  a  marked  degree.  Moreover,  the  quantity  which 
is  produced  varies  with  the  immediate  needs  of  the  economy  and  bears  a 
reciprocal  relationship  to  the  quantity  of  heat  formed  in  other  structures,1 
and  is  regulated  apparently  by  specific  nerve-centres. 

When  the  muscles  are  contracting  less  than  one-fifth  of  the  energy  appears 
as  work,  and  more  than  four-fifths  as  heat.  The  contractions  of  the  heart  also 
furnish  an  appreciable  percentage  of  heat  as  an  accompaniment  of  contraction; 
and  considerable  heat  is  formed  indirectly  by  the  resistance  offered  by  the 
the  blood-vessel  walls  to  the  blood  current.  Indeed,  the  entire  work  of  the 
heart  becomes  converted  into  heat,  representing  approximately  5  to  10  per 
cent,  of  the  total  heat-production.  The  quantity  formed  as  by-products  of 
tin-  activity  of  various  structures  during  a  state  of  muscular  quiet  is  doubtless 
small  compared  with  the  quantity  produced  by  the  muscles. 

The  Thermogenic  Nerves  <ni</  ( 'entres. — Heat-production  may  occur  independ- 
ently of,  but  under  normal  circumstances  it  is  regulated  by,  the  nervous  system. 
A  muscle  separated  from  all  nervous  influences  continues  to  produce  heat,  but  con- 
siderably less  than  before,  and  it  ceases  to  respond  to  the  demands  of  the  system 
for  more  or  less  beat  as  do  muscles  with  their  nerves  intact.  Injuries  to  certain 
part-  of  the  cerebro-s pinal  axis  affect  heat-production  in  muscles,  in  some  in- 
stances causing  an  increase  and  in  others  a  decrease;  but  these  changes  do  not  occur 
if  the  nervous  communication  between  the  centre.-  and  muscles  is  destroyed. 

Thermogenic  Nerves. — Specific  ther genie  nerve-fibres  have  not  as  yet 

been  i-olated,  although  the  researches  of  Kemp,2  Reichert,3  Schultz,4  and 
others  indicate  that  such  fibre-  exist.  In  the  skeletal  muscles  probably 
three  independent  kinds  of  processes  go  on  which  produce  heat,  one  subser- 
vient to  the   contraction-   of  the   mii-dcs.  as  observed   in   locomotion,  etc. ; 

1  Riibner:  Sitzungsberichte  d.  kimigl.  Bayer.  Akad.  der  Wi&semchaft,  1885,  Heft  4. 

Therapeutic  Oazette,  L889,  |>.  1  •">">. 
3  Ibid.,  1891,  p.  151. 
1  Schultze:   Archiv  fur  experimentelle  Pathologic  und  Pharmakologie,  1899,  Bd.  43,  S.  193. 


ANIMAL   HEAT.  4Ul 

another  in  the  form  of  contraction  known  as  shivering  ;  and  a  third,  giving 
rise  to  heat  as  the  only  important  phenomenon.  The  heat  produced  by 
muscles  in  ordinary  or  general  muscular  acts  and  in  repair  and  growth  is  a 
mere  incident  to  activity;  but  the  heat  arising  during  shivering  is  undoubt- 
edly a  specific  product — i.  e.,  the  object  of  the  shivering  is  a  production  of 
heat  (see  p.  433).  If  the  nerve-fibres  which  convey  the  impulses  tli.it  cause 
shivering  be  ordinary  motor  fibres,  then  these  fibres  are  not  only  motor  film-, 
but  specific  thermogenic  fibres  in  so  far  as  they  are  connected  with  heat- 
production  by  this  act.  There  are  also,  apparently,  fibres  which  are  entirely 
distinct  from  the  motor  fibres,  and  which  convey  impulses  that  give  rise  to 
heat-production  as  a  specific  product,  and  even  in  the  entire  absence  of  motor 
phenomena.  Thus,  in  a  curarized  animal  in  which  all  motor  activity  of  the 
skeletal  muscles  is  abolished,  an  enormous  increase  of  heat-production  may 
occur  (Reichert)  which  cannot  satisfactorily  be  explained  in  any  other  way 
than  by  assuming  the  existence  of  such  specific  thermogenic  fibres.  Our 
information  at  present  is,  however,  so  limited  that  we  can  do  scarcely  more 
than  speculate. 

Our  knowledge  of  the  character  of  the  afferent  fibres  which  carry  impulses 
that  reflexly  affect  thermogeuesis  is  very  unsatisfactory.  There  can  be  no 
doubt  that  sensory  impulses  arise  in  various  parts  of  the  organism,  especially  in 
the  skin,  which  exercise  important  influences  upon  the  heat-producing  pro- 
cesses. Thus,  cooling  the  skin  reflexly  excites  heat-production,  which  cannot 
be  attributed  to  indirect  influences  upon  other  functions,  but  whether  or  not 
there  exist  specific  afferent  thermogenic  fibres  is  not  known.  It  is  possible  that 
the  temperature  nerves  of  the  skin,  the  cold  and  the  heat  nerves,  may  be 
responsible  for  reflex  excitation  or  depression  of  heat-production. 

The  Thermogenic  Centres. — The  existence  of  specific  thermogenic  centre-  has 
for  many  years  been  conceded,  but  it  has  only  been  recently  that  hypothesis 
has  given  place  to  fact.  The  most  important  results  of  recent  research  may  be 
generalized  as  follows:  (1)  That  the  irritation  of  the  skin  by  heat  or  cold  is 
followed  by  marked  changes  in  thermogeuesis,  which  effects  are  to  a  certain 
extent  entirely  independent  of  vasomotor  and  other  incidental  changes,  and 
which,  therefore,  are  due  in  part  to  an  increase  of  heat-production  dependent 
directly  upon  efferent  thermogenic  impulses.  (2)  That  injury  or  excitation  of 
certain  parts  of  the  brain  is  followed  by  an  increase  of  heat-production.  (3) 
That  injury  or  excitation  of  certain  other  parts  of  the  brain  is  followed  by 
diminished  heat-production.  (4)  That  injury  of  the  spinal  cord  may  be  fol- 
lowed by  an  increase  or  decrease  of  heat-production  which  cannot  be  entirely 
accounted  for  by  vaso-motor  and  other  attendant  alterations.  (5)  That  after 
operations  upon  certain  parts  of  the  cerebro-spinal  axis  their  follows  an  increase 
or  decrease  in  the  quantity  of  0O2  formed,  indicating  a  corresponding  effed  <>n 
the  heat-producing  processes. 

The  results  of  recent  calorimetric  work  show  that  there  are  definite  regions 
of  the  cerebro-spinal  axis  which  are  apparently  specifically  concerned  in  ther- 
mogenesis;  that  the  effects  of  excitation  or  destruction  of  each  region  are  more 


492  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

or  less  characteristic ;  and  that  the  different  regions  seem  to  be  so  intimately 
related  to  one  another  as  to  constitute  a  co-ordinate  mechanism.  Certain  of  these 
regions  when  irritated  give  rise,  as  a  direct  result,  to  increased  thermogenesis, 
hence  they  are  of  the  nature  of  thermo-accelerator  centres;  and  others  to 
diminished  thermogenesis,  hence  are  thermo-inhibitory  centres.  Both  kinds  of 
centres  seem  to  be  associated  with  and  to  govern  a  third  kind  which  is  dis- 
tinguished as  the  general  or  automatic  thermogenic  centres.  The  mechanism 
may  be  theoretically  expressed  in  this  form:  The  general  thermogenic  centres 
may  be  regarded  as  maintaining  by  virtue  of  independent  activity  a  fairly  con- 
stant standard  of  thermogenesis,  and  as  being  influenced  to  increased  activity  by 
the  thermo-accelerator  centres  and  to  diminished  activity  by  the  thermo-inhib- 
itory centres.  The  finer  or  smaller  variations  iu  thermogenesis  are  presumably 
effected  by  the  general  centres,  whereas  the  grosser  variations  are  probably  ef- 
fected by  the  influences  of  the  thermo-accelerator  and  thermo-inhibitory  centres. 

Specific  heat-centres  (thermogenic  and  thermolytic)  have  by  various  ob- 
servers been  held  to  exist  in  certain  regions  of  the  brain  cortex,  in  the  base  of 
the  brain  just  in  front  of  and  beneath  the  corpus  striatum,  in  the  corpus  stri- 
atum, in  the  septum  lucidum  and  the  tuber  cinereum,  in  the  optic  thalamus, 
in  the  corpora  quadrigemina,  in  the  pons  and  medulla  oblongata,  and  in  the 
spinal  cord.  Some  of  these  centres  have  been  regarded  as  being  thermogenic 
and  others  as  being  thermolytic.  Many  errors  in  deduction  have,  however, 
been  made  because  of  the  many  inherent  difficulties  attending  experimenta- 
tion upon  the  cerebro-spinal  axis,  and  because  almost  all  the  methods  used 
necessarily  involve  injury  or  excitation  of  contiguous  parts.  The  methods 
adopted  of  studying  these  various  regions  have  been  chiefly  destruction  or 
injury  by  means  of  a  probe,  actual  cautery,  excision,  and  the  injection  of 
cauterants;  by  transverse  incisions  across  the  cerebro-spinal  axis  so  as  to  sepa- 
rate higher  from  lower  portions  of  the  cerebro-spinal  axis;  and  by  excitation 
by  small  punctures,  electricity,  etc. 

In  classifying  these  centres  Ave  are  governed  by  the  results  which  follow 
excitation  and  destruction.  When  irritation  or  destruction  directly  affects 
thermogenesis,  the  centre  is  regarded  as  being  thermogenic,  but  if  heat-dissi- 
pation is  the  process  directly  affected,  the  centre  is  regarded  as  being  thermo- 
lytic. In  classifying  thermogenic  centres  we  would  regard  the  centre  as  being 
a  general  thermogenic  centre  if  it  is  capable,  after  the  destruction  of  other 
thermogenic  centres,  of  causing  the  normal  output  of  heat;  a  thermo-acceler- 
ator  centre  is  distinguished  by  the  lad  that  excitation  increases  thermogenesis, 
while  destruction  does  not  diminish  thermogenesis,  unless  the  centre  happens 
to  be  active  at  the  time,  and  further  by  the  fact  that  after  its  destruction  the 
normal  output  of  heal  may  continue;  a  thermo-inhibitory  centre  is  distinguished 
by  a  decrease  of  heat-production  following  stimulation  and  by  the  absence  of 
any  permanent  effect  on  thermogenesis  when  the  centre  is  destroyed.  The 
general  or  reflex  thermogenic  centres  are  undoubtedly  continuously  active,  the 
degree  of  activity  varying  according  to  the  immediate  demands  of  the  organism 
for  heat  ;  while  the  thermo-accelerator  and  thermo-inhibitory  centres  are  prob- 


ANIMAL    HEAT.  493 

ably  only  intermittently  active,  coming  into  play  when  the  general  centres  are 
of  themselves  unable  to  effect  a  sufficiently  rapid  compensation. 

While  it  must  be  admitted  that  our  knowledge  of  the  precise  locations, 
physiological  peculiarities,  and  correlations  of  the  thermogenic  centres  is  by  no 
means  complete,  we  have  at  our  disposal  some  most  important  and  significant 
data.  The  general  thermogenic  centres  have  been  shown  by  Reichert 1  to  be 
located  in  the  spinal  cord.  The  thermogenic  centres  in  the  brain  are  either 
thermo-accelerator  or  thermo-inhibitory.  Thermo-accelerator  centres  probably 
exist  in  the  caudate  nuclei  (possibly  also  in  the  tuber  cinereum  and  optic 
thalami),  pons,  and  medulla  oblongata.2 

Excitation  of  any  one  of  these  regions  is  followed  by  a  pronounced  rise  of 
heat-production  ;  destruction  of  any  one  region  may  or  may  not  be  followed 
by  a  decrease  of  heat-production,  and  if  a  decrease  does  occur  it  may  in  most 
cases  be  attributed  to  incidental  causes,  such  as  shock  and  other  attendant 
conditions.  The  centre  which  is  common  to  the  pons  and  medulla  is  for  the 
most  part  probably  located  in  the  latter,  but  it  is  not  so  powerful  in  its  influ- 
ences on  thermogenesis  as  the  thermo-accelerator  centres  in  the  basal  regions 
of  the  cerebrum.  These  cerebral  centres  are  affected  by  agents  which  have 
little  or  no  effect  on  the  heat  centres  of  the  spinal  cord.  Thermo-inhibitory 
centres  have  been  located  in  the  dog  in  the  region  of  the  sulcus  cruciatus  and 
at  the  junction  of  the  supra-sylvian  and  post-sylvian  fissures.3  Irritation 
of  either  of  them  is  followed  by  a  decrease  of  heat-production,  while  their 
destruction  may  be  followed  by  a  transient  increase  of  heat-production.  The 
cruciate  centre  is  the  more  powerful.  None  of  these  cerebral  centres  exercises 
any  influence  on  thermogenesis  after  section  of  the  spinal  cord  at  its  junction 
with  the  medulla  oblongata. 

Theoretically,  these  centres  are  associated  in  this  way  :  The  general  thermo- 
genic centres  are  in  the  spinal  cord,  and  while  they  are  perhaps  impressionable 
to  impulses  coming  to  them  through  various  sensory  nerves,  they  are  not 
apparently  in  the  least  influenced  by  cutaneous  impulses  caused  by  change-  in 
external  temperature  nor  by  changes  of  the  temperature  of  the  blood.  It  is 
not  improbable  that  these  centres  are  in  the  anterior  cornua  of  the  spinal  cord. 
The  thermo-accelerator  and  thermo-inhibitory  centres  are  connected  with  the 
general  centres  by  nerve-fibres,  the  former  influencing  the  general  centres  to 
increased  activity,  and  the  latter  to  diminished  activity.     The  thermo-accel- 

1  University  Medical  Magazine,  1894,  vol.  v.  p.  406. 

2  Reichert:  University  Medical  Magazine,  1894,  vol.  6,  p.  303.  Ott :  Journal  of  Nervous  and 
Mental  Diseases,  1884,  vol.  11,  ]>.  141;  1887,  vol.  14,  p.  154;  1888,  vol.  15,  p.  85 ;  Therapeutic 
Gazette,  1887,  p.  592;  Fever,  Thermotaxia,  <ni<l  Oalorimetry,  1889.  Aronsohn  and  Sachs:  Pfluger's 
Archiv  fur  Physiologie,  1885,  Bd.  37,  S.  232.  Girard:  Archives  de  Physiologic  normale  el  patholo- 
gique,  1886,  t.  8,  p.  281.  Baginsky  und  Lehmann  :  Virchovfs  Archiv  fw  Physiologie,  1886,  Bd 
106,  8.  258.  White:  Journal  of  Physiology,  1890,  vol.  11,  p.  1  ;  1891,  vol.  12,  p.  233.  Baculo: 
Centri  temici,  1890,  1891,  and  1892.  Tangl :  Pfiiiger's  Archiv  fur  rinisini„;,ie,  1895,  Bd.  OS,  S.  559. 
Schultze:  Archiv  fur  experimentelle  Pathologic  und  Pharmakologie,  1890,  Bd.  43,  S.  193. 

3  Wood:  "Fever"  Smithsonian  Coutrihutions  to  Knowledge,  1880,  No.  357.  Ott:  Journal  of 
Nervous  and  Mental  Diseases,  1888. 


[94  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

erator  and  thermo-inhibitory  centres  seem  to  be  especially  affected  by  cuta- 
neous impulses  which  arc  generated  by  changes  in  external  temperature,  and 
to  be  influenced  by  alterations  of  the  temperature  of  the  blood.     It  is  doubtless 

through  thes intres  that  changes  in  external  and  internal  temperature  are 

able  to  affect  the  heat-producing  processes.  Presumably  both  an  increase  of 
temperature  of  the  blood  and  cutaneous  impulses  generated  by  an  increase  of 
external  temperature  excite  the  thermo-inhibitory  centres,  and  thus  inhibitory 
impulses  are  senl  to  the  general  centres,  lessening  their  activity;  on  the  other 
hand,  both  a  fall  of  temperature  of  the  blood  and  cutaneous  impulses  gener- 
ated by  cold  presumably  excite  the  thermo-accelerator  centres  and  thus  cause 
impulses  to  be  sent  to  the  general  centres,  exciting  them  to  greater  activity. 

The  Mechanism  concerned  in  Thermolysis. — The  loss  of  heat  by  the  body 
is  in  a  large  measure  incidental  to  attendant  conditions  and  is  not  a  reflex 
result  of  the  activity  of  a  thermolytic  mechanism;  in  other  words,  the  loss 
occurs  essentially  by  virtue  of  the  same  conditions  as  would  cause  inanimate 
bodies  to  lose  heat.  The  living  homothermous  organism  differs  as  regards  the 
loss  of  heat  from  dead  matter,  chiefly  in  that  the  rapidity  with  which  heat- 
dissipation  occurs  is  regulated  to  a  material  extent  by  vital  processes.  The 
regulation  of  the  loss  of  heat  is  effected  by  the  operations  of  a  complex  mech- 
anism— that  is,  one  consisting  of  a  number  of  distinct  although  correlated  parts. 
A  study  of  this  mechanism,  which  is  designated  the  thermolytic  mechanism, 
includes  a  consideration  of  all  of  the  processes  by  which  heat  is  lost,  of  the 
nervous  mechanisms  which  govern  them,  and  of  the  conditions  which  affect 
them,  but  especially  of  those  processes  and  mechanisms  which  act  reciprocally 
in  conjunction  with  the  thermogenic  mechanism  to  maintain  the  mean  bodily 
temperature.  Practically  all  of  the  heat  lost  by  the  organism  occurs  by  radia- 
tion and  conduction  from  the  skin,  by  the  evaporation  of  water  from  the  skin 
and  lungs,  and  in  warming  the  food,  drink,  and  inspired  air.  From  these  facts  we 
believe  that  mechanisms  which  affect  the  blood-supply  to  the  skin,  the  quantity 
of  sweat  secreted,  the  condition  of  the  surface  of  the  skin,  and  the  quantity  of 
air  inspired  must  in  a  large  measure  regulate  thermolysis.  For  instance,  if  the 
temperature  of  the  organism  be  materially  increased  there  occur  increased  activ- 
ity  of  the  heart,  peripheral  vascular  dilatation,  increased  respiratory  activity,  and 
(except  in  fever)  an  increase  in  the  secretion  of  sweat.  The  increase  of  the 
activity  of  the  heart  together  with  the  dilatation  of  the  cutaneous  blood-vessels- 
increases  the  quantity  of  blood  supplied  to  the  skin  ;  the  cutaneous  blood-vessels 
are  dilated,  exposing  a  larger  surface  of  blood  to  the  cooler  external  surround- 
ings, and  thus  materially  favoring  the  loss  of  heat  by  radiation  ;  the  increase  in 
the  quantity  of  sweat  is  favorable  loan  increase  in  the  amount  of  water  evaporated, 
and  thus  to  a  larger  loss  of  heat  in  this  way;  an  increase  of  respiratory  activity 
means  a  larger  volume  of  air  respired,  a  greater  expenditure  of  heat  in  warming 
the  air  and  in  the  evaporation  of  water  from  the  lungs.  In  man  the pilo-motor 
mechanism  plays  a  subsidiary  and  unimportant  part  in  the  regulation  of  heat- 
dissipation,  but  in  some  lower  animals,  as  in  certain  birds,  it  is  of  considerable 
importance.     The  thermolytic  mechanism  therefore  includes  the  cardiac,  vaso- 


ANIMAL   HEAT.  495 

motor,  respiratory,  sweat,  and  pilo-motor  mechanisms.  All  these  are  affected 
directly  or  indirectly  by  the  temperature  of  the  blood  and  skin.  An  increase 
in  the  temperature  of  the  blood  and  skin  excites  all  of  them  so  that  changes 
are  brought  about  which  favor  heat-loss.  The  respiratory  movements  especially 
may  be  rendered  intensely  active,  and  in  certain  animals  to  such  a  marked 
degree  that  they  may  become  more  frequent  than  the  heart-beats. 

Thermotaxis. — Thermotaxis  or  heat-regulation  is  effected  by  reciprocal 
changes  in  heat-production  and  heat-dissipation  brought  about  by  the  inter- 
vention of  the  thermogenic  and  thermolytic  centres,  just  as  the  regulation 
of  arterial  pressure  is  effected  by  the  reciprocal  relations  of  the  cardiac 
and  vaso-motor  mechanisms.  If  heat-production  is  more  active  than  heat- 
dissipation,  thermolysis  is  so  affected  that  the  heat-loss  is  increased,  and  thus 
the  mean  bodily  temperature  maintained  ;  if  heat-production  is  subnormal, 
heat-dissipation  also  falls.  Similarly,  if  heat-dissipation  is  increased,  the 
heat-producing  processes  are  excited  to  greater  activity  to  make  up  the  loss ; 
conversely,  if  heat-dissipation  is  decreased,  heat-production  also  tends  to  be 
decreased.  These  reciprocal  actions  depend  essentially  or  wholly  upon  the 
influence  of  cutaneous  impulses  and  the  temperature  of  the  blood.  For 
instance,  an  increase  of  the  temperature  of  the  blood  increases  the  activity 
of  the  thermolytic  processes,  thus  effecting  a  compensation.  If  we  subject  an 
animal  to  a  moderately  cold  atmosphere,  as  in  the  winter,  heat-dissipation  is 
increased,  but  cutaneous  impulses  are  generated  which  excite  the  thermogenic 
centres  so  that  heat-production  is  also  increased,  and  thus  the  bodily  temperature 
is  maintained  practically  unaffected.  It  is  only  under  abnormal  conditions  or 
under  conditions  of  intense  muscular  activity  that  this  reciprocal  relation- 
ship is  so  disturbed  that  changes  in  one  process  are  not  quickly  compensated 
for  by  changes  in  the  other. 

Thermotaxis  is  effected  in  a  large  measure  reflexly,  especially  by  cutaneous 
impulses  generated  by  external  cold  and  heat,  both  thermogenic  and  thermo- 
lytic processes  being  affected.  Cold  applied  temporarily,  as  in  the  form  of  a 
douche,  bath,  sponging,  etc.,  causes  constriction  of  the  cutaneous  capillaries. 
This  lessens  both  the  quantity  and  temperature  of  the  blood  passing  through 
the  skin,  the  effect  of  which  tends  to  decrease  the  dissipation  of  heat  by  radia- 
tion and  conduction.  Moreover,  a  lessened  blood-supply  causes  the  skin  to 
become  poorer  in  fluid,  so  that  the  conduction  of  heat  from  the  warmer  inner 
parts  is  lessened.  The  conductivity  of  the  skin  is  further  decreased  by  the 
action  of  the  pilo-motor  muscles,  which  when  in  contraction  or  in  a  state  of 
greater  tonicity  render  the  skin  tenser  and  thus  press  out  the  blood  and  tissue 
juices.  The  secretion  of  sweat  is  diminished,  so  that  the  quantity  of  heat  lost 
in  the  vaporization  of  water  is  decreased.  On  the  other  hand,  heat-dissipation 
tends  to  be  materially  increased  by  the  greater  radiation  of  heat  due  to  the 
greater  difference  between  the  temperature  of  the  body  and  of  the  douche,  bath, 
etc.,  and  the  tendency  to  an  increase  in  this  way  is  much  greater  than  the 
opposite  tendency  depending  upon  the    factors   above   noted,  therefore   heat- 


496  AN   AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

dissipation  is  increased.  Bathing  the  skin  with  cold  water  increases  heat-loss 
by  the  vaporization  of  water  as  well  as  by  conduction. 

The  excitation  of  the  cutaneous  nerves  by  cold  reflexly  increases  thermo- 
genesis, and  to  such  an  extent  thai  heat-production  may  even  exceed  the 
quantity  dissipated,  thus  causing  an  increase  of  bodily  temperature.  This  rise, 
which  is  transient,  may  amount  to  0.2'  Cor  more,  and  is  followed  by  a  re- 
action in  which  the  temperature  may  tall  0.2°  C.  or  more  below  the  normal,  and 
continue  subnormal  for  some  hum-;  this  fall  in  turn  is  succeeded  by  a  supple- 
mentary reaction  in  which  the  temperature  may  rise  slightly  above  the  normal. 

The  chief  reactions  brought  about  by  moderate  external  cold  are  constriction 
of  the  cutaneous  blood-vessels,  a  diminution  of  the  quantity  of  sweat  secreted, 
increased  tonicity  of  the  pilo-motor  muscles,  and  increased  tonicity  of  the 
skeletal  muscles.  The  action  upon  the  latter  muscles  may  be  so  marked  as 
to  cause  shivering,  which  increases  respiratory  activity  (see  p.  432)  and 
presumably  similarly  increases  heat-production. 

Moderate  external  heat  causes  dilatation  of  the  cutaneous  vessels,  excites 
the  genera]  circulation  and  thus  increases  the  blood-supply  to  the  skin,  excites 
respiratory  movements  and  the  sweat-glands,  but  decreases  thermogenesis. 
Owing  to  the  dilatation  of  the  blood-vessels  of  the  skin  and  the  excitation  of 
the  circulation  the  temperature  and  the  quantity  of  the  blood  supplied  to  the 
skin  are  increased,  so  thai  condition-  are  caused  which  are  favorable  to  an 
increased  loss  of  heat  by  radiation,  [ncreased  activity  of  the  respiratory 
movements  mean-  a  larger  volume  of  air  respired,  and  consequently  a  greater 
loss  of  heat  in  warming  the  air  and  in  the  evaporation  of  the  larger  quantity 
of  water  from  the  lungs.  The  increase  in  the  quantity  of  sweat  formed  also 
favors  heat-dissipation  by  means  of  the  lamer  amount  of  water  evaporated 
from  the  skin.  External  heat  also  causes  diminished  tonicity  of  the  muscles, 
and  consequent  diminished  thermogenesis  which  is  probably  due  to  a  lessening 
of  the  activity  of  the  chemical  changes  in  the  muscles. 

When  external  temperature  is  excessive  and  continued,  heat-regulation  is 
rendered  impossible  :  if  extreme  cold,  heat-dissipation  takes  place  more  rapidly 
than  heat-production,  so  that  bodily  temperature  falls  until  death  results;  if 
extreme  heat,  heat-dissipation  is  so  interfered  with  that  heat  accumulates 
within  the  organism,  causing  a  continuous  rise  of  temperature  which  finally 
causes  death. 

Abnormal  Thermoiaxis. — By  this  term  is  meant  the  regulation  of  the  heat- 
processes  under  conditions  in  which  the  mean  bodily  temperature  is  maintained 
:it  ;i  standard  above  or  below  the  normal,  a-  in  fever  and  in  animals  from 
which  the  hair  has  been  shaved.  It  is  assumed  that  under  normal  conditions 
the  beat-centres  are  "set,"  as  it  were,  for  a  given  temperature  of  the  blood, 
and  that  when  the  temperature  of  the  blood  goes  above  or  below  this  standard 
a  compensatory  reaction  occur.-,  so  that  thermogenesis  and  thermolysis  are 
properly  affected  to  bring  about  an  adjustment.  In  fever  it  may  be  considered 
that  the  centres  are  set  for  a  higher  temperature  than  the  normal ;  the  higher 
the  fever,  the  higher  the  adjustment.     The  centre-  may  beset  for  subnormal 


ANIMAL    HEAT.  497 

temperatures,  as  in  the  case  of  a  rabbit  shaved,  whose  temperature  may  remain 
2°  or  3°  below  the  normal  for  a  week  or  more.  When  the  cause  of  the  ab- 
normal condition  disappears,  the  centres  are  readjusted  to  the  normal  standard. 

E.  Post-mortem  Rise  of  Temperature. 

A  rise  of  temperature  after  death  is  not  uncommon;  indeed,  in  ease  of 
violent  death  of  healthy  individuals,  and  after  death  following  convulsions, 
a  rise  in  temperature  is  almost  invariable.  This  increase  is  due  to  continued 
heat-production  and  to  diminished  heat-dissipation.  Heat-production  after 
death  may  be  due  to  continued  chemical  activity  in  the  muscles  and  other 
structures  which  are  not  dead  but  simply  in  a  moribund  state.  There  is,  as  it 
were,  a  residual  metabolic  activity  which  remains  in  the  cells  until  their  tem- 
perature has  been  reduced  to  such  a  standard  that  the  molecular  transforma- 
tions cease — in  other  words,  until  the  death  of  the  cells  occurs.  Consequently, 
the  higher  the  temperature  of  the  individual  at  the  time  of  somatic  death  (the 
cessation  of  the  circulation  and  respiration),  the  longer  heat-production  con- 
tinues, because  the  longer  the  time  required  to  cool  the  cells  to  such  a  degree 
that  their  chemical  processes  no  longer  go  on.  Heat  is  also  produced  during 
the  development  of  rigor  mortis.  The  more  quickly  rigor  sets  in,  and  the 
more  intense  it  is,  the  greater  is  the  abundance  of  heat  produced. 

The  tendency  to  an  increase  of  bodily  temperature  is  favored  by  the  marked 
diminution  of  heat-dissipation  which  occurs  immediately  upon  the  cessation 
of  the  circulation  and  respiration.  Therefore,  while  both  heat-production  and 
heat-dissipation  fall  at  once  and  enormously  at  the  time  of  death,  heat-dissipa- 
tion may  be  decreased  to  a  more  marked  degiee  than  heat-production,  so  that 
heat  may  accumulate  and  the  bodily  temperature  rise. 

Temperature  Sense. — (See  Cutaneous  Sensibility,  in  the  section  on  Special 
Senses.) 

Vol.  l.—Vi 


IX.  THE  CHEMISTRY  OF  THE  ANIMAL  BODY. 


Introduction. — Living  matter  contains  hydrogen,  oxygen,  sulphur,  chlo- 
rine, iodine,  fluorine,  nitrogen,  phosphorus,  carbon,  silicon,  potassium,  sodium, 
calcium,  magnesium,  and  iron.  Abstraction  of  one  of  these  elements  means 
death  to  the  organism.  The  compounds  occurring  in  living  matter  mav  for 
the  most  part  be  isolated  in  the  laboratory,  but  they  do  not  then  exhibit  the 
properties  of  animate  matter.  In  the  living  cell  the  smallest  particles  of  matter 
are  arranged  in  such  a  manner  that  the  phenomena  of  life  are  possible.  Such 
an  arrangement  of  materials  is  called  protoplasm,  and  anything  which  disturbs 
this  arrangement  results  in  sickness  or  in  death.  Somatic  death  may  result 
from  physical  shock  to  the  cell;  or  it  may  be  due  to  the  inability  of  the  cell  or 
the  organism  to  remove  from  itself  poisonous  products  which  are  retained  in 
the  body  so  affecting  the  smallest  particles  that  functional  activity  is  impossible. 
Pure  chemistry  adds  much  to  our  knowledge  of  physiology,  but  it  must  always 
be  remembered  that  the  conditions  present  in  the  beaker  glass  are  not  the  con- 
ditions present  in  the  living  cell,  for  physical  and  chemical  results  are  de- 
pendent on  surrounding  conditions ;  hence  the  necessity  and  value  of  animal 
experimentation.  From  chemical  changes,  the  physical  activities,  i.  e.  the 
motions  characteristic  of  life,  result.  Hence  the  chemistry  of  protoplasm  is 
the  corner-stone  of  biology.  The  plan  of  this  section  is  designed  to  consider 
the  substances  concerned  in  life  in  the  order  usually  followed  by  chemical 
text-books,  and  to  compare  as  far  as  possible  the  results  obtained  in  pure 
chemistry  with  the  chemical  changes  in  the  organism. 

The  Non-metallic  Elements. 
Hydrogen,  H  =  l. 

This  gas  is  found  as  a  constant  product  of  the  putrefaction  of  animal 
matter,  and  is  therefore  present  in  the  intestinal  tract.  It  is  found  in  the 
expired  air  of  the  rabbit  and  other  herbivorous  animals,  and  in  traces  in  the  ex- 
pired air  of  carnivorous  animals,  having  first  been  absorbed  by  the  blood  from 
the  intestinal  tract.  By  far  the  greater  amount  of  hydrogen  in  the  animal 
and  vegetable  worlds,  as  well  as  in  the  world  at  large,  occurs  combined  in  the 
form  of  water,  and  it  will  be  shown  that  the  proteids,  carbohydrates,  and  fate, 
characteristic  of  the  organism,  all  contain  hydrogen  originally  derived  from 
water.  In  the  atmosphere  is  found  ammonia  in  traces,  which  holds  hydrogen 
in  combination,  and  this  is  a  second  source  of  hydrogen,  especially  for  the  con- 
struction of  the  proteid  molecule. 

Preparation. — (1)  Through  the  electrolysis  of  water,  by  which  one  volume 

499 


500  AN   AMEBICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

of  oxygeo  is  evolved  od  the  positive  pole  and  two  volumes  of  hydrogen  on  the 
negative. 

(2)  Through  the  action  of  zinc  on  sulphuric  acid,1 

Zn  ;   ILSO,      ZnS04  +  IL. 

(3)  Through  putrefaction  (by  which  is  understood  the  change  effected  in 
organic  matter  through  certain  lower  organisms,  bacteria) hydrogen  i.s  liberated 
in  the  intestinal  canal  from  proteid  matter,  and  especially  from  the  fermenta- 
tion of  carbohydrates : 

C6Hu06  =  C4H802     2C02  +  2H2. 

Sugar.        Butyric  acid. 
In  putrefaction  in  the  presence  of  oxygen   the  hydrogen  formed  immediately 
unites   with   oxygen,  producing  water;   hence,  notwithstanding  the  enormous 
amount  of  putrefaction   in   the  world,  there  is  no  accumulation  of  hydrogen 
in  the  atmosphere. 

Both  bacteria  and  an  enzynu  can  liberate  hydrogen  by  acting  on  calcium  formate, 
Ca(CHOa)s  ll<>  CaC03  +  C02  +  2H2, 
and  this  same  reaction  may  be  brought  aboul  by  the  action  of  metallic  iridium,  rhodium, 
or  ruthenium  on  formic  acid.  Anenzyrm  is  a  substance  probably  of  proteid  nature  capa- 
ble of  producing  change  in  ether  substances  without  itself  undergoing  apparent  change 
(example,  pepsin).  Bunge*  calls  attention  to  the  fact  that  the  above  reaction  may  he  brought 
about  by  living  cells  (bacterial,  by  an  organic  substance  (enzyme),  and  by  an  inorganic 
metal.  This  similarity  of  action  between  organized  and  unorganized  material,  between 
living  and  dead  substances,  is  shown  more  and  more  conspicuously  as  science  advances. 

Properties. — Hydrogen  burns  in  the  air,  forming  water,  and  if  two  volumes 
of  hydrogen  and  one  of  oxygen  be  ignited,  they  unite  with  a  loud  explosion. 
Hydrogen  will  not  support  respiration,  but,  mixed  with  oxygen,  may  be 
respired,  probably  being  dissolved  in  the  fluids  of  the  body  as  an  inert  gas, 
without  effect  upon  the  organism.  Hydrogen  may  pass  through  the  intes- 
tinal tissues  into  the  blood-vessels,  according  to  the  laws  of  diffusion,  in  ex- 
change for  some  other  gas,  and  may  then  be  given  off  in  the  lungs.  Nascent 
hydrogen — that  is  to  say,  hydrogen  at  the  moment  of  generation — is  a  powerful 
reducing  agent,  uniting  readily  with  oxygen  (see  p.  505). 

Oxygen,  0  =  16. 

Oxygen  is  found  free  in  the  atmosphere  to  the  amount  of  about  21  per 
cent,  by  volume,  and  is  found  dissolved  in  water  and  chemically  combined  in 
arterial  blood.  It  is  swallowed  with  the  food  and  may  be  present  in  the  stom- 
ach, but  it  entirely  disappears  in  the  intestinal  canal,  being  absorbed  by  respir- 
atory  exchange  through  the  mucous  membrane.  It  ocean's  chemically  com- 
bined with  metals  80  that  it  forms  one-hall'  the  weight  of  the  earth's  crust  ; 
it  likewise  occurs  combined  in  water  and  in  most  of  the  materials  forming 
animal  and  vegetable  organisms.      It  is  found  in  the  blood  in  loose  chemical 

1  It   is  not  within  the  scope  of  this  work   to  <.'ive  more  than  typical  methods  of  lahoratory 
preparation.      For  greater  detail   the   reader  is  referred  to  works  on  general   chemistry. 
1  Physiolfxjuchi  Chemie,  2d  ed.,  L889,  i>.  167. 


THE    CHEMISTRY    OE    THE   ANIMAL    BODY.  501 

combination  as  oxyhemoglobin.  It  is  present  dissolved  in  the  saliva,  so  great 
is  the  amount  of  oxygen  furnished  by  the  blood  to  the  salivary  gland ;  it 
is,  however,   not  found  in  the  urine  or  in  the  bile. 

Preparation. — (1)  Through  the  electrolysis  of  water  (see  Hydrogen). 

(2)  By  heating  manganese  dioxide  with  sulphuric  acid, 

I'MnO,  -  H2S04  =  2MnS04  +  2H20  +  02. 

(3)  By  heating  potassium  chlorate. 

2KC103  =  2KCl+302. 

(4)  By  the  action  of  a  vacuum,  or  an  atmosphere  containing  no  oxygen,  on 
a  solution  of  oxyhemoglobin, 

Hb-02=Hb+02. 

This  latter  is  the  method  occurring  in  the  higher  animals.  Any  oxygen  present 
in  a  cell  in  the  body  combines  with  the  decomposition  products  formed  there, 
consequently  entailing  in  such  a  cell  an  oxygen  vacuum,  which  now  acts  upon 
the  oxyhemoglobin  of  the  blood-corpuscles  in  an  adjacent  capillary,  dissociating 
it  into  oxygen  and  hemoglobin. 

(5)  Bv  the  action  of  sunlight  on  the  leaf  of  the  plant,  transforming  the 
carbonic  oxide  and  water  of  the  air  into  sugar,  and  setting  oxygen  free, 

6C02  +  6H20  =  C6H1206  +  602. 

Properties. — All  the  elements  except  fluorine  unite  with  oxygen,  and  the 
products  are  known  as  oxides,  the  process  being  called  oxidation.  It  is  usually 
accompanied  by  the  evolution  of  energy  in  the  form  of  heat,  and  often  the 
energy  liberated  is  sufficiently  great  to  cause  the  production  of  light.  The 
light  of  a  candle  comes  from  vibrating  particles  of  carbon  in  the  flame,  which 
particles  collect  as  lampblack  on  a  cold  plate.  In  pure  oxygen  combustion  is 
more  violent  than  in  the  air;  thus,  iron  burns  brilliantly  in  pure  oxygen,  while 
in  damp  air  it  is  only  very  slowly  converted  into  oxide  (rust).  This  latter 
process  is  called  slow  combustion,  and  animal  metabolism  is  in  the  nature  of  a 
slow  combustion.  In  the  burning  candle  has  been  noted  the  liberation  of  heat, 
and  motion  of  the  smallest  particles  :  in  the  cell  there  is  likewise  oxidation,  with 
dependent  liberation  of  heat  and  motion  of  the  smallest  particles  in  virtue  of 
which  the  cell  is  active.  Phenomena  of  life  are  phenomena  of  motion,  and 
the  energy  supplying  this  motion  comes  from  chemical  decomposition.  The 
amount  of  oxidation  in  the  animal  is  not  increased  in  an  atmosphere  of  pure 
oxygen,  nor,  within  wide  limits,  is  it  affected  by  variations  in  atmospheric 
pressure,  for  oxygen  is  not  the  cmtse  of  decomposition.  In  putrefaction  it  is 
known  that  bacteria  cause  decomposition,  and  the  products  subsequently  unite 
with  oxygen.  But  the  cause  of  the  decomposition  in  the  cell  remains  unsolved, 
it  being  only  known  that  the  decomposition-products  after  being  formed  unite 
with  oxygen.  So  the  quantity  of  oxygen  absorbed  by  the  body  depends  on  the 
decomposition  going  on,  not  the  decomposition  on  the  absorption  of  oxygen. 
This  distinction  is  fundamental  (see  further  under  Ozone  and  Peroxide  of 
Hydrogen). 


502  J.V   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

By  reduction  in  it-  simplest  sense  is  meant  the  removal  of  oxygen  wholly 
or  in  part  from  the  molecule.  Example:  reduced  haemoglobin  from  oxy- 
hsemoglobin,  iron  from  oxide  of  iron  ( Fc.Og).  Reduction  may  likewise  be 
accomplished  by  Bimple  addition  of  hydrogen  to  the  molecule,  or  by  the  sub- 
stitution of  hydrogen  for  oxygen.  These  two  processes  may  be  represented 
respectively  by  the  reactions : 

CH3CHO    +H2   =CH3CH2OH. 

Ethyl  aldehyde.  Ethyl  alcohol. 

ciLcoolI      2H2     (!I,('IL()M+H20. 

Acetic  acid.  Ethyl  alcohol. 

Ozone,  03. — Ozone  is  a  -econd  form  of  oxygen  possessing  more  active  oxi- 
dizing  properties  than  common  oxygen.  It  is  found  in  neighborhoods  where 
large  quantities  of  water  evaporate,  and  after  a  thunder-storm. 

Preparation. — (1)  An  induction  current  in  an  oxygen  atmosphere  breaks  up  some  of 
the  molecules  present  into  atoms  of  nascenl  or  ■"active"'  oxygen  — 0 — ,  the  powerful 
affinities  of   whose  free  bonds  enter  into  combination  with  oxygen,   0  =  0  to  form 

Q 

ozone.    /\ 

(2)  Through  the  slow  oxidation  of  phosphorus, 

P2  +  3H20  +  202  -  2H3PO3  +  (-0-). 
(-0-)  +  02  =  Os. 

(3)  On  the  positive  pole  in  the  electrolysis  of  water. 

In  each  of  the  above  cases  ozone  is  formed  by  the  action  of  nascent  oxygen  on  oxygen. 

Properties. — Ozone  is  a  colorless  gas,  hardly  soluble  in  water,  and  having 
the  peculiar  smell  noted  in  the  air  after  thunder-storms.  Ozone  has  powerful 
oxidizing  properties  due  to  its  third  unstable  atom  of  oxygen,  oxidizing  silver, 
which  oxygen  of  itself  doe-  not.  Bui  ozone  is  not  as  oxidizing  as  nascent  or 
'"active"  oxygen,  which  may  convert  carbon  monoxide  into  dioxide,  and 
nitrogen  into  nitrons  acid.  Ozone  cannot  occur  in  the  cell,  as  any  nascent 
oxygen  formed  would  naturally  unite  not  with  oxygen,  but  with  the  more 
readily  oxidizable  materials  of  the  cell  itself.  Ozone  acts  on  an  alcoholic  solu- 
tion of  guaiacum,  turning  it  blue;  blood-corpuscles  give  the  same  reaction 
with  guaiacum,  hence  it  was  thought  that  haemoglobin  converted  oxygen  into 
ozone.  However,  this  test  is  uol  a  test  for  ozone,  but  for  "active"  atomic 
oxygen,  which  is  produced  from  the  ozone  and  in  the  decomposing  blood-cor- 
puscle (see  theory  of  Traube  below,  and  that  of  Hoppe-Seyler  under  Peroxide 
of  Hydrogen).     Ozone  converts  oxyhemoglobin  into  methaemoglobin. 

Theory  of  Traube  as  to  the  ('mis,  of  Oxidation  in  the  Body. — Indigo-blue 
dissolved  in  a  sugar-solution  gives  up  oxygen  in  the  atomic  state  for  the  oxida- 
tion of  sugar,  and  the  solution  becomes  white.  If  shaken  in  the  air  the  blue 
coloration  reappears,  owing  to  the  absorption  of  oxygen  by  the  indigo.  Hence 
indigo  has  the  power  of  splitting  oxygen  into  atom-,  and  acts  as  an  "oxygen- 
carrier"  between  the  air  and  the  sugar.  Traube  is  of  the  opinion  that  an 
"oxygen-carrier"  exists  in  the  blood-corpuscles.  Sugar  i-  destroyed  by  stand- 
ing in  fresh  defibrinated  blood  ;  serum  alone  doe-  not  effect  this,  nor  does  a 
solution  of  oxyhemoglobin,  but    it    may  take   place  in  the  extract  obtained  by 


THE   CHEMISTRY   OF   THE  ANIMAL   BODY.  503 

the  action  of  a  0.6  per  cent,  sodium-chloride  solution  on  blood -corpuscles.1 
The  action  here  has  been  described  as  that  of  catalysis,  that  is,  an  action  by 
which  some  substance  effects  decomposition  in  another  substance  without  per- 
manent change  in  itself.  In  this  case  the  substance  in  the  blood-corpuscle 
is  defined  as  an  "  ox ygen-carrier,"  taking  molecules  of  oxygen  from  oxy- 
hemoglobin and  giving  atomic  oxygen  for  the  oxidation  of  the  sugar. 
Spitzer2  has  shown  that  these  oxygen-carriers  are  iron-containing  nucleo- 
proteids  which  are  characteristic  constituents  of  the  cellular  nucleus.  Hence 
the  nucleus  is  the  principal  oxidation  organ  of  living  matter.  Separation  of 
protoplasm  from  its  nucleus  causes  the  death  of  the  protoplasm  on  account 
of  decreased  oxidative  capacity.3 

Old  turpentine  is  highly  oxidizing.  This  action  was  once  believed  to  be  due  to  absorbed 
ozone.  If  old  turpentine  be  mixed  with  water  and  filtered,  the  aqueous  extract  has  the 
same  properties,  due  to  the  fact  that  an  oxidized  product  which  is  soluble  in  water,  gives 
off',  under  favorable  conditions,  atomic  oxygen.  * 

Water,  H20. — Water  is  found  on  the  earth  in  large  quantities,  and  its 
vapor  is  a  constant  constituent  of  the  atmosphere.  It  is  a  product  of  the 
combustion  of  animal  matter,  and  occurs  in  expired  air  almost  to  the  point  of 
saturation.  It  is  furthermore  given  off  by  the  kidneys  and  by  the  skin.  It 
is  a  necessary  constituent  of  a  living  cell,  and  forms  67.6  per  cent,  of  the 
weight  of  the  human  body  (Moleschott).  Removal  of  5  to  6  per  cent,  of 
water  from  the  body,  as  for  example  in  cholera,  causes  the  blood  to  become 
very  viscid  and  to  flow  slowly,  no  urine  is  excreted,  the  nerves  become  excess- 
ively irritable,  and  violent  convulsions  result.5 

Preparation. — (1)  Bypassing  an  electric  spark  through  a  mixture  of  one  volume  of 
oxygen  and  two  volumes  of  hydrogen. 

(2)  By  the  combustion  of  a  food — as,  for  example, 

C6H1206  +  120  =  60O2  +  6H20. 

Sugar. 

(3)  Distilled  water  is  made  in  quantity  by  boiling  ordinary  water  and  condensing  the 
vapors  formed  in  another  vessel. 

Properties. — Water  is  an  odorless,  tasteless  fluid  of  neutral  reaction,  colorless 
in  small  quantities,  but  bluish  when  seen  in  large  masses.  It  is  a  bad  conductor 
of  heat  and  electricity.  It  conducts  electricity  better  when  it  contains  .silts. 
It  is  nearly  non-compressible  and  nun-expansible;  thus  in  plant-life,  through 
evaporation  on  the  surface  of  the  leaf,  sap  is  continuously  attracted  from  the 
mots  of  the  tree.  The  solvent  properties  of  water  give  to  the  blood  many  of 
its  uses,  soluble  foods  being  carried  to  the  tissues  and  soluble  products  of 
decomposition   to   the   proper  organs  for  elimination. 

When  water  is  absorbed  by  any  substance  the  process  is  called  hydration, 

1  Read  W.  Spitzer  :   Pflugefa  Arehiv,  1S95,  Bd.  60,  S.  307.         2  Tbid.,  1897,  Bd.  67,  S.  615. 
3  J.  Loel>:   Arrliir  fin-  ErUwickelwngsmechanik  der  Organismen,  1899,  Bd.  8,  8.  689. 
*  N.  Kowalewsky :  Centralblatt  fiir  die  medicinische  Wissenschaft,  1889,  S.  113. 
5C.  Voit:  Hermann's  Handbuch,  1881,  Bd.  vi.  1,  S.  349. 


504  -l.V    AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

as  an  example  of  which  may  be  cited  the  change  of  calcium  oxide  into 
hydroxide  when  thrown  into  water.  When  a  substance  breaks  down  into 
simpler  bodies  through  absorption  of  water  the  process  is  called  hydrolysis  or 
hydrolytic  cleavage.  Thus  cane-sugar  may  take  up  water  and  be  resolved  into 
a  mixture  of  dextrose  and  levulose,  which  are  called  cleavage-products.  So, 
likewise,  starch  and  proteid  are  resolved  into  series  of  simpler  bodies  through 
hydrolytic  cleavage — changes  which  take  place  in  intestinal  digestion.  All 
forms  of  fermentation  and  putrefaction  are  characterized  by  hydrolysis  (exam- 
ple-, p.  500),  and  hence  complete  drying  prevents  such  processes.  Alcoholic, 
butyric,  and  lactic  fermentation  are  apparent  though  not  real  exceptions  to  the 
above.  Alcoholic  fermentation,  for  example,  is  usually  represented  by  the 
reaction,  C6H1206  =  2C2H5OH  +  2C( ).,,  but  the  C02  is  in  fact  united  with 
water,  and    hence   the  true  reaction   should   read, 

C6H1206  -  2H20  =  2CJT5OH  +  2H2C03. 

Sugar.  Alcohol. 

Drinking-water  contains  salts  and  air  dissolved,  giving  it  an  agreeable  taste. 
One  does  not  willingly  take  distilled  water  on  account  of  its  tastelessness. 

Dry  animal  membranes  and  cells  absorb  water  in  quantities  varying  with  the  concentra- 
tion and  the  quality  of  salts  in  the  solution  in  which  they  are  suspended  (Liebig).  This  is 
called  imbibition.  Membranes  will  absorb  a  solution  of  potassium  salts  in  greater  quantity 
than  of  sodium  salts,  and  so  the  potassium  salts  are  found  predominating  in  the  cells,  the 
sodium  salts  in  the  fluids  of  the  body.  A  blood-corpuscle  treated  with  distilled  water 
swells  because  it  can  hold  more  distilled  water  than  it  can  salt-containing  plasma.  A  cor- 
puscle placed  in  a  0.65  percent,  solution  of  sodium  chloride  (the  physiological  salt-solution) 
remains  unchanged,  for  this  corresponds  in  concentration  to  the  plasma  of  the  blood.  If 
the  corpuscle  he  placed  in  a  strong  solution  of  a  salt  it  shrivels,  because  it  cannot  hold  as 
much  of  that  solution  as  it  can  one  having  the  strength  of  the  salts  of  the  plasma.  Oysters 
are  often  planted  at  the  mouths  of  fresh-water  rivers,  since  they  imbibe  more  of  the  weaker 
solution  and  appear  fatter.  If  salt  lie  placed  on  meat  and  left  to  itself,  a  brine  is  formed 
around  the  meat  on  account  of  the  osmotic  pressure  exerted  by  the  strong  solution  of 
-alt.  which  sets  up  an  osmotic  stream  of  water  to  the  salt  and  thus  deprives  the  meat  of 
water. 

Different  bodies  require  different  quantities  of  heat  to  warm  them  to  the  same  extent. 
The  amount  of  heat  required  to  raise  the  temperature  of  water  is  greater  than  that  for  any 
other  substance.  A  calorie  or  heat-unit  is  the  amount  of  heat  required  to  raise  1  cubic 
centimeter  of  water  from  0°  to  1°  ('.  The  specific  heat  of  the  human  body— that  is,  the 
amount  of  heat  required  to  raise  1  gram  1°  C— is  about  0.8  that  of  water.  On  the  trans- 
formation  of  a  substance  from  the  Bolid  to  the  liquid  state,  a  certain  amount  of  heat  is 
absorbed,  known  as  latent  li<<it.  To  melt  1  gram  id'  ice  producing  1  gram  of  water  at  0°, 
79  calories  are  required,  or  sufficient  to  raise  1  gram  of  water  from  0°  to  79°.  Upon  the 
basis  of  these  facte  a  determination  may  be  made  by  means  of  the  ice-culorimeter  of  the 
number  of  heat-units  produced  in  the  combustion.  For  example,  1  gram  of  sugar (dex- 
trose)  burned  in  an  ice-chamber,  melts  19.86  m-ams  of  ice.  Since  each  gram  required 
79  calories  to  melt  it,  3939  calories  must  have  been  produced  altogether.  If  1  gram  of 
sugar  he  burned  in  the  body,  the  heat  produced  is  identically  the  same,  and  maybe  meas- 
ured with  great  accuracy.1 

In  the  transformation  of  water  at  100   to  steam  at  100°  there  is  a  further  absorption  of 

1  M.  Rubner:  Zeitachrift fur  Biologic,  1893,  Bd.  .30,  S.  73. 


THE    CHEMISTRY   OF    THE   ANIMAL    BODY.  505 

heat,  the  latent  heat  of  steam.  For  1  gram  of  water  this  absorption  amounts  to  536.5 
calories.  This  property  of  water  is  of  great  value  to  life,  for  through  the  heat  absorbed  in 
the  evaporation  of  sweat  the  temperature  of  the  body  is  in  part  regulated. 

Peroxide  of  Hydrogen,  H202,  is  found  in  very  small  quantities  in  the  air, 
in  rain,  snow,  and  sleet,  and  where  there  is  oxidation  of  organic  matter. 
Preparation. — (1)  By  the  action  of  sulphuric  acid  on  peroxide  of  barium, 
Ba02  +  H2S04  =  BaS04  +  H,< >,. 

(2)  Peroxide  of  hydrogen  is  a  product  of  the  oxidation  of  phosphorus,  and  generally 
exists  wherever  ozone  is  produced. 

(3)  Peroxide  of  hydrogen  exists  wherever  nascent  hydrogen  acts  on  oxygen. 
It  is  therefore  found  mixed  with  hydrogen  evolved  at  the  negative  pole  in  the 
electrolysis  of  water.  This  action  happens  in  putrefaction,  where  the  nascent 
hydrogen  unites  with  any  oxygen  present,  and  the  resulting  H202  strongly 
oxidizes  the  organic  matter  through  the  free  — O —  atom  liberated.1 

Properties. — Peroxide  of  hydrogen  is  a  colorless,  odorless,  bitter-tasting 
fluid,  which  decomposes  slowly  at  20°  F.,  and  with  great  violence  at  higher 
temperatures.  It  oxidizes  where  ordinary  oxygen  is  ineffective  ;  it  is  a  powerful 
bleaching  agent,  and  is  used  to  produce  blonde  hair.  It  destroys  bacteria.  Blood- 
corpuscles  brought  into  a  solution  of  H202  bring  about  its  rapid  decomposition 
into  water  and  atomic  oxygen,  whereby  oxygen  is  evolved  and  oxyhemoglobin 
is  converted  into  methsemoglobin.  If  oxyhemoglobin  be  brought  into  a 
putrefying  fluid,  the  nascent  hydrogen  withdraws  oxygen  from  combination 
to  form  H202,  and  then  the  atomic  oxygen  reacts  on  haemoglobin  to  form 
methaemoglobin.2  The  formula  for  the  peroxide  is  probably  II — O — O — H. 
In  certain  cases  peroxide  of  hydrogen  has  a  reducing  action. 

Theory  of  Hoppe-Seyler3  to  account  for  the  Oxidation  in  the  Body. — This 
maintains  that,  as  in  putrefaction,  hydrogen  is  produced  in  the  decomposition 
of  the  cell,  and  acting  on  the  oxygen  present  converts  it  into  peroxide  with 
its  unstable  atom,  which  then  splits  off  as  active  oxygen  and  effects  the  oxida- 
tion of  the  substances  in  the  cell.  This  theory  is  easier  to  reconcile  with  the 
fact  that  oxidation  is  dependent  on  the  amount  of  decomposition  (see  p.  501) 
than  is  the  theory  of  Traube. 

Solutions  of  H202  do  not  liberate  iodine  from  potassium  iodide  immediately,  but  only 
on  the  addition  of  blood-corpuscles  or  of  ferrous  sulphate,  which  cause  liberation  of — 0 — , 
and  then  any  starch  present  may  be  colored  blue  (see  p.  502).  Gruaiacum  is  not  affected 
by  H,02  unless  blood-corpuscles  or  ferrous  sulphate  be  added  to  make  the  oxygen  active. 

Sulphur,  S  =  32. 

Sulphur  is  built  in  the  proteid  molecule  of  the  plant  from  the  sulphates 
taken  from  the  ground.  It  is  found  in  albuminoids,  especially  in  keratin.  As 
taurin  it  occurs   in   muscle  and   in  bile,  as   iron   and   alkaline  sulphide  in  the 

1  Hoppe-Seyler:  Zeitschrift  fur  physwlogische  Chemie,  1878,  Bd.  '_\  8.  22. 

2  Hoppe-Seyler,  Op.  cit.,  S.  26. 

3  P0ijir.<  ArchiVf  Bd.  L2,  S.  16,  1876.  See  also  Berichte  der  deutschen  ehemischen  QaeUaehqfl, 
Bd.  22,  S.  2215. 


506  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

feces,  as  sulphuretted  hydrogen  in  the  intestinal  gas,  as  sulphate  and  other 
unknown  compounds  in  the  urine. 

Sulphuretted  Hydrogen,  II..S. — This  gas  is  found  in  the  intestines,  and 
pathologically  in  the  urine. 

Preparation. — (1)   Action   of   hydrochloric  or   sulphuric   acid  on  ferrous 

sulphide, 

FeS  +  H2SG4  =  FeS04  +  H2S. 

This  same  reaction  takes  place  by  treating  feces  (which  contain  FeS)  with  acid. 

(2)  From  the  putrefaction  of  proteids,  and  by  boiling  proteid  with  mineral 
acid. 

Properties. — Sulphuretted  hydrogen  unites  readily  with  the  alkalies  and 
with  iron  salts,  forming  sulphide;  hence  little  H2S  is  found  in  the  intestinal 
tract.  It  is  a  strong  poison  when  respired.  It  has  been  shown  to  enter  into 
combination  with  oxyhemoglobin  to  form  sulph-hsemoglobin,  and  likewise 
in  frogs  it  rapidly  kills  the  nerves.1  Sulphuretted  hydrogen  diluted  with 
hydrogen  and  introduced  into  the  rectum  of  a  dog  produces  symptoms  of 
poisoning  in  one  to  two  minutes  (Planer).  It  has  an  offensive  odor  similar 
to  foul  eggs. 

Sulphurous  Acid,  H2SO:!. — This  acid  has  been  found  in  the  urine  of  cats  and  dogs, 
and  lias  been  detected  by  Striimpell  in  human  urine  in  a  case  of  typhoid  fever. 

Sulphuric  Acid,  H2S04. — This  acid  is  found  in  the  urine  in  combination 
with  alkali  (preformed  sulphate),  and  with  indol,  skatol,  cresol,  and  phenol 
(ethereal  sulphates).     It  is  found  in  the  saliva  of  various  gastropods. 

Preparation. — (1)  By  oxidation  of  sulphur  with  nitric  acid, 

S  +  2HND3  =  H2S04  +  2NO. 

(2)  By  oxidation  of  sulphur-containing  proteid, 

Properties. — Sulphuric  acid  is  a  very  powerful  acid.  It  is  produced  in  the 
body  by  the  burning  of  the  proteids  (which  contain  0.5  to  1.5  per  cent.  S), 
80  per  cent,  or  more  being  oxidized  to  acid,  while  the  remainder  appears  in  the 
urine  in  the  unoxidized  condition  termed  neutral  sulphur.  When  proteid,  fat, 
and  starch  free  from  ash  are  fed  to  dogs,  they  live  only  half  as  long  as  they 
would  were  they  starving,2  for,  according  to  Bunge,3  the  sulphuric  acid  formed 
abstracts  necessary  salts  from  the  tissue.  (For  further  discussion  of  this  see 
pp.  354  and  525). 

Tf  100  cubic  centimeters  of  urine  be  treated  with  5  cubic  centimeters  of  hydrochloric 
a<-id  and  barium  chloride  be  added,  the  'preformed  sulphuric  acid  is  precipitated  as  barium 
sulphate  (BaSOJ,  which  may  be  washed,  dried,  and  weighed.  It'  100  cubic  centimeters 
of  urine  be  mixed  with  an  equal  volume  <>t'  a  Bolution  containing  barium  chloride  and 
hydrate,  filtered,  and  one-half  the  fill  rate  (  =  50  cubic  centimeters  of  urine,  now  free  of 
preformed  Bulphate)  be  strongly  acidified  with  hydrochloric  acid  and  boiled,  the  ethereal 
sulphates  will  be  broken  up,  and  the  resulting  precipitate  of  barium  sulphate  will  corre- 
spond to  the  ethereal  sulphuric  acid.     To  determine  the  neutral  sulphur,  evaporate  the 

1  Harnack  :  Archiv  fur  expervmenteUe  Paihdogie,  wnd  Pharmakofogie,  1894,  Bd.  34,  S.  156. 
2 .1.  Foster:  Zeitschrifijur  Biologie,  1873,  Bd.  9,  S.  297. 
3  Physiologische  Chemie,  2d  ed.,  1889,  p.  104. 


THE   CHEMISTRY  OF  THE  ANIMAL   BODY.  507 

urine  to  dryness,  fuse  the  residue  with  potassium  nitrate  (KN0:t),  which  oxidizes  all  the 
sulphur  to  sulphate,  take  up  with  water  and  hydrochloric  acid,  add  barium  chloride,  and 
the  precipitate  (BaSOj  represents  the  total  sulphur  present.  Deduct  the  amount  belong- 
ing to  sulphuric  acid,  previously  determined,  and  the  remainder  represents  the  neutral 
sulphur. 

Metabolism  of  Sulphur. — The  total  amount  of  sulphur  in  the  urine 
runs  proportionally  parallel  with  the  amount  of  nitrogen  ;  that  is  to  say,  the 
amount  is  proportional  to  the  amount  of  proteid  destroyed.  The  amount  of 
ethereal  sulphate  is  dependent  upon  the  putrefactive  production  of  indol, 
skatol,  phenol,  and  cresol  in  the  intestinal  canal,  which  on  absorption  form  a 
synthetical  combination  with  the  traces  of  sulphate  in  the  blood.  Concerning 
neutral  sulphur  it  is  known  that  taurin  is  one  source  of  it.  If  taurin  be  fed 
directly,  the  amount  of  neutral  sulphur  in  the  urine  increases  (Salkowski),  and 
in  a  dog  with  a  biliary  fistula  the  neutral  sulphur  decreases  but  does  not  en- 
tirely disappear.1  In  a  well-fed  dog  with  a  biliary  fistula  Yoit2  found  the 
quantity  of  sulphur  in  the  bile  to  be  about  10  to  13  per  cent,  of  that  in  the 
urine.  This  biliary  sulphur  (taurin)  is  normally  reabsorbed,  as  the  quantity 
of  sulphur  in  the  feces  (FeS,  Na2S)  is  small  and  derived  principally  from  pro- 
teid putrefaction.  The  amount  of  neutral  sulphur  in  the  urine  is  greatest 
under  a  meat  diet,  least  when  fat  or  gelatin  is  fed;  the  sulphur  of  gelatin 
is  very  small  in  quantity.  In  dyspncea  the  amount  of  neutral  sulphur  in- 
creases in  the  urine,  on  account  of  insufficient  oxidation.3  The  neutral  sul- 
phur of  the  urine  includes  potassium  sulphocyanide  (originally  derived  from 
the  saliva),  likewise  a  substance  which  on  treatment  with  calcium  hydrate 
yields  ethyl  sulphide,  (C2H5)2S,4  and  there  are  present  other  unknown  com- 
pounds (see  p.  547).  When  an  animal  eats  proteid  and  neither  gains  nor 
loses  the  same  in  his  body,  the  amount  of  sulphur  ingested  is  equal  to  the 
sum  of  that  found  in  the  urine  and  feces.  If  sulphur  be  eaten,  it  partially 
appears  as  sulphate  in  the  urine.  Sulphates  eaten  pass  out  through  the  urine. 
They  play  no  part  in  the  life  of  the  cell. 

Chlorine,  CI  =  35.5. 

Free  chlorine  is  not  found  in  the  organism,  and  when  1  neat  lied  it  vigor- 
ously attacks  the  respiratory  mucous  membranes.  Chlorine  is  found  combined 
in  the  body  as  sodium,  potassium,  and  calcium  chlorides,  as  hydrochloric  acid, 
and  it  is  said  to  belong  to  the  constitution  of  pepsin.8 

Hydrochloric  Acid,  HC1,  is  found  to  a  small  extent  in  the  gastric  juice. 

Preparation. — (1)  If  sunlight  acts  on  a  mixture  of  equal  volumes  of  chlorine  and 
hydrogen,  they  unite  with  a  loud  explosion. 

1  Kunkel :  Archivfur  </i><  gesammte  Physiologic,  1877,  Bd.  14,  S.  353. 

2  Zeitsekrifi  fur  Biologie,  1894,  Bd.  30,  S.  554. 

3  Harnack  and  Kleine:  Zeitachrift  fur  Biologie,  1899,  Bd.  37,  S.  417. 

4  J.  J.  Abel  :  Kitsch  rift  fur  physiologisehe  ('hemic,  1894,  1!<1.  'Jo,  S.  253. 

5  E.  O.  Schoumow  -Simanowski :  Archiv  fiir  exper.  Pathologie  und  Pharmakologie,  1894,  Bd. 
33,  S.  336. 


508  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

(2)  By  the  art  ion  of  strong  sulphuric  acid  on  common  salt. 

L'XaCl  +  H2S04  =  Na2S04  +  2HC1. 

(3)  By  the  action  of  primary  acid  phosphate  of  sodium  on  common  salt, 

NaCl      NaH2P04  =  Na2HP04  +  HCl. 

This,  according  to  Maly,  represents  the  process  in  the  cells  of  the  gastric  glands. 
Properties. — Hydrochloric  acid  readily  unites  with  most  metals,  forming 
chlorides.  It  causes  a  gelatinization  of  the  proteids  and  seems  to  unite  with 
them  chemically.  Such  gelatinization  is  a  necessary  forerunner  of  peptic  di- 
gestion. The  cleavage  products  of  peptic  digestion  (peptones,  proteoses,  etc.) 
combine  with  more  hydrochloric  acid  than  the  original  more  complex  proteid.1 
Free  hydrochloric  acid  of  the  strength  of  the  gastric  juice  (0.2  per  cent.) 
inverts  cane-sugar  at  the  temperature  of  the  body,2  and  inhibits  the  action  of 
bacteria.  Hydrochloric  acid  is  derived  from  decomposition  of  chlorides  in 
the  secreting  cells  of  the  stomach.  It  has  been  shown  that  the  excretion  of 
common  salt  in  the  urine  is  decreased  during  those  hours  that  the  stomach  is 
active,  while  the  acidity  of  the  urine  decreases.  If,  in  a  dog  with  a  gastric 
fistula,  the  mucous  membrane  of  the  stomach  be  stimulated  and  the  gastric 
juice  be  removed  as  soon  as  formed,  the  urine  becomes  strongly  alkaline  with 
sodium  carbonate  (the  excess  of  Na  liberated  taking  this  form)  while  the  chlo- 
rides may  entirely  disappear  from  the  urine.3  Respiration  in  an  atmosphere 
containing  0.5  per  cent.  HC1  gas  becomes  very  uncomfortable  after  twelve 
minutes/ 

It'  the  bases  (K,  Na.  Ca.  M>.r,  Fe)  of  gastric  juice  and  then  the  acid  radicals  (CI  and 
P205)  be  determined,  and  the  phosphoric  anhydride  be  united  with  the  proper  bases,  and 

then  chlorine  with  the  rest  of  the  bases,  there  still  remains  an  excess  of  chlorine  which  can 
only  have  belonged  to  the  hydrochloric  acid  present.  To  detect  free  hydrochloric  acid  put 
three  or  four  drops  of  a  saturated  alcoholic  solution  of  tropseolin  00  in  a  small  white  porcelain 
cover,  add  to  this  an  equal  quantity  of  gastric  juice,  evaporate  slowly,  and  the  presence 
of  hydrochloric  acid  is  shown  by  a  beautiful  violet  color,  not  given  by  any  organic  acid.5 
Griinzburg's  reagent  consisting  of  phloroglucin  and  vanillin  in  alcoholic  solution,  warmed 
(as  above)  with  gastric  juice  containing  tree  hydrochloric  acid,  gives  a  carmine-red 
mirror  on  the  porcelain,  not  given  by  an  organic  acid.6 

CHLORINE  in  THE  body  is  ingested  as  chloride,  and  leaves  the  body  as 
such,  principally  in  the  urine,  likewise  through  the  sweat  and  tears,  and  in 
traces  in  the  feces. 

Bromine,  Br  =  80. 

Salts  of  bromine  are  found  in  marine  plants  and  animals,  but  their  physiological  im- 
portance has  not  been    established.     Bromine  is  a  fluid  of  intensely  disagreeable  odor, 

1  Chittenden:  Qartwrighl  Lectures  on  Digestive  Proteolysis,  1895,  p.  52. 

*  Ferris  and  Lusk :  American  Journal  of  Physiology,  1898,  vol.  i.  p.  277. 

3  E  O.  Schoumow-Simanowski :  Arckiv  fur  a/per.  Pathologie  und  Pharmakologie,  1894,  Bd. 
33,  S.  336. 

*  Lehmann  :  Archiv  fur  Hygiene,  Bd.  5,  S.   1. 

'  Boas:  Deutsche medicinische  Wocketnschrift,  1887,  No.  39. 
'•  <  iiinzburg  :   Centralblatt  fiir  Iclinische  Medicin,  1887,  No.  40. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  509 

whose  vapors  strongly  attack  the  skin,  turning  it  brown,  and  likewise  the  mucous  mem- 
branes of  the  respiratory  passages. 

Hydrobromic  Acid,  HBr,  may  be  prepared  by  the  action  of  water  on  phosphorus 
tribromide, 

PBr3  +  3H20  -  3HBr  +  H3P03. 

It  is  a  colorless  gas  of  penetrating  odor.  If  sodium  bromide  be  given  to  a  dog  in  the 
place  of  sodium  chloride,  fifty  per  cent,  and  more  of  the  hydrochloric  acid  may  be  sup- 
planted by  hydrobromic  acid  in  the  gastric  juice.1  The  various  organs  are  then  found  to 
contain  bromine,  especially  the  kidneys'  through  which  it  may  be  eliminated. 

Iodine,  I  =  127. 

Like  bromine,  the  salts  of  iodine  ai'e  found  in  many  marine  plants  and  animals,  espe- 
cially in  the  algae.  It  is  found  in  the  thyroid  gland.  Iodine  is  prepared  in  metallic-looking 
plates,  almost  insoluble  in  water,  but  soluble  in  alcohol  (tincture  of  iodine).  Iodine  is  still 
more  strongly  corrosive  in  its  action  on  animal  tissue  than  is  chlorine  or  bromine,  and  is  an 
antiseptic  and  disinfectant.     A  slight  trace  of  free  iodine  turns  starch  blue. 

Hydriodic  Acid,  HI,  is  prepared  like  hydrobromic  acid,  by  the  action  of  water  on 
tri-iodide  of  phosphorus.  An  aqueous  solution  of  hydriodic  acid  introduced  into  the 
stomach  is  absorbed,  and  shortly  afterward  iodine,  as  alkaline  iodide,  may  be  detected 
in  the  urine.  On  administration  of  sodium  iodide  to  a  dog  with  his  food,  only  very 
little  hydriodic  acid  appears  in  the  gastric  juice.* 

Circulation  in  the  Body. — Iodine  or  iodides  given  are  rapidly  eliminated  in  the 
urine,  in  smaller  amounts  in  saliva,  gastric  juice,  sweat,  milk,  etc.  It  is  noticed  that  ti  »r 
weeks  after  the  administration  of  the  last  dose  of  potassium  iodide,  traces  of  iodine  are 
found  in  the  saliva,  and  none  in  the  urine.  The  explanation  lies  in  the  presumption  that 
iodine  has  been  united  with  proteid  to  a  certain  extent,  and  appears  in  such  secretions  as 
saliva,  which  contains  materials  derived  from  proteid  through  glandular  manufacture.4 
A  similar  explanation  avails  in  the  case  of  Drechsel's5  discovery  that,  in  patients  who 
have  been  treated  with  iodides,  iodine  may  be  detected  in  the  hair  (the  keratin  of  hair 
being  derived  from  other  proteid  bodies.)  Whether  free  iodine  or  hydriodic  acid  is  liber- 
ated in  the  tissues  from  ingested  iodides  are  disputed  points.  Baumann6  discovered  an 
organic  compound  of  iodine  occurring  in  the  thyroid  gland  and  containing  as  much  as  9.3 
percent,  of  iodine.  Roos7  states  that  this  thyroiodine  from  sheep's  thyroid  constantly 
contains  about  5  per  cent,  of  iodine.  When  fed  it  increases  the  metabolism  of  proteid  and 
fat8  and  acts  as  an  antitoxine.  According  to  Blum,9  the  iodine  is  combined  with  the  pro- 
teids  of  the  thyroid  in  varying  quantity,  and  any  liberated  iodine  may  act  within  the  thy- 
roid to  destroy  toxic  bodies,  especially  nerve  toxines.10  Oswald,11  on  the  contrary,  states 
that  the  effective  principle  of  the  thyroid  is  a  thyroglobulin  containing  L.66  per  cent,  of 
iodine.  This  thyroglobulin  treated  with  acids  yields  thyroiodine.  which  contains  14.4 
per  cent,  of  iodine.  Thyroids  which  contain  no  iodine  have  no  physiological  effect 
upon  metabolism.12 

1  Nencki  and  Schoumow-Simanowski :  Arehivfiir  exper.  Pathologie  wnd  Pharmakologie,  1895, 
Bd.  34,  S.  320. 

2  Rosenthal:  Zeitschrift fur physiologische  Chemie,  1896,  Bd.  22,  S.  227. 

3  Nencki  and  Schoumow-Simanowski :  Lor.  cit. 

*  Schmiedeberg :  Qrundriss  der  Arzeinmittellehre,  2d  ed.,  1888,  S.  197. 

5  Cailralblatt  fur  Physiologic,  1896,  Bd.  9,  S.  704. 

6  Zeitschrift  fur  physiologische  Chemie,  1895,  Bd.  21,  S.  319.       7  Ibid.,  1898,  Bd.  25,  S.  1. 
8  Voit,  F. :  Zeitschrift  fur  Biologie,  1897,  Bd.  35,  S.  116. 

»  Zeitschrift  fiir  physiologische  Chemie,  1898,  Bd.  26,  S.  160. 

10  Blum:  Pfluger'a  Archiv,  1899,  Bd.  77,  S.  70. 

11  Zeitschrift  fiir  physiologische  ('/ionic,  1899,  Bd.  27,  S.  14. 
u  Boss,  E. :  Ibid.,  1899,  Bd.  28,  S.  40. 


510  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

Fluorine,  F  =  19. 

Fluorine  is  found  in  the  bones  and  teeth,  in  muscle,  brain,  blood,  and  in 
all  investigated  tissues  of  the  body,  though  in  minute  quantities.  In  one  liter 
of  milk  0.0003  gram  of  fluorine  have  been  detected.1  Fluorine  is  found  in 
plants,  and  in  soil  without  fluorine  plants  do  not  flourish.  It  seems  to  be  a 
necessary  constituent  of  protoplasm.  Free  fluorine  is  a  gas  which  cannot  be 
preserved,  as  it   unite-  with  any  vessel  in  which  it  is  prepared. 

Hydrofluoric  Acid,  1II\  is  prepared  by  heating  a  fluoride  with  concentrated  sul- 
phuric acid,  in  a  platinum  or  lead  dish. 

CaF,+  HaS04  =  CaS04  +  2HF. 

Properties.  — Hydrofluoric  acid  is  a  colorless  gas,  so  powerfully  corrosive  that  breathing 
its  fumes  results  fatally.  Its  aqueous  solutions  are  stable,  but  can  be  kept  only  in  vessels 
of  platinum,  gold,  lead,  or  india-rubber.  It  etches  glass,  uniting  to  form  volatile  silicon 
fluoride, 

Si02  +  4HF  =  SiF4-f-2H20. 

Circulation  in  the  Body. — Tappeiner  and  Brandl2  have  shown,  on 
feeding  sodium  fluoride  (NaF)  to  a  dog  in  doses  varying  between  0.1  and 
1  gram  daily,  that  the  fluorine  fed  was  not  all  recoverable  in  the  urine  and 
feces,  but  was  partially  stored  in  the  body.  On  subsequently  killing  the  dog, 
fluorine  was  found  in  all  the  organs  investigated,  and  was  especially  found  in 
the  dry  skeletal  ash  to  the  extent  of  5.19  per  cent,  reckoned  as  sodium  fluoride. 
From  the  microscopic  appearance  of  the  crystals  seen  deposited  in  the  bone,  the 
presence  of  calcium  fluoride  was  concluded.  In  this  form  it  normally  occurs 
iu  bones  and  teeth. 

Nitrogen,  N  =  14. 

Free  nitrogen  constitutes  79  per  cent,  of  the  volume  of  atmospheric  air.  It 
is  found  dissolved  in  the  fluids  and  tissues  of  the  body  to  about  the  same  extent 
as  distilled  water  would  dissolve  it.  It  is  swallowed  with  the  food,  may  par- 
tially diffuse  through  the  mucous  membrane  of  the  intestinal  tract,  but  forms 
a  considerable  constituent  of  any  final  intestinal  gas.  It  is  found  in  the  atmos- 
phere combined  as  ammonium  nitrate  and  nitrite,  which  are  useful  in  furnish- 
ing the  roots  of  the  plant  with  material  from  which  to  build  up  proteid. 
Bacteria  upon  the  roots  of  certain  vegetables  combine  and  assimilate  the  free 
nitrogen  (.ft  he  air  (Hellriegel  and  Willforth).     Cultures  of  alga  do  the  same.3 

Preparation. — (1)  By  abstraction  of  oxygen  from  air  through  burning  phosphorus  in 
a  bell  jar  over  water,  pentoxide  of  phosphorus  being  formed,  which  dissolves  in  the  water 
and  almost  pure  nitrogen  remains. 

_•    By  heating  nitrite  of  ammonium, 

NH4NO,  =  2N+-2B  O. 

Properties. — Nitrogen  is  especially  distinguished  by  the  absence  of  chemical 
affinity  for  other  element-.     It  does  not  support  combustion,  and  in  it  both  a 

1  i  i.  Tammann  :  Zeitschrifi  fiir  physiologiseht  Chemie,  1888,  Bd.  12,  S.  322. 

5  ZeUachrifi  fur  Biologic,  1892,  Bd  28,  S.  518. 

3  P.  Kosaowitch :   Botaniaehe  Zeitung,  L894,  Jahrg.  50,  S.  97. 


THE    CHEMISTRY    OF    THE   ANIMAL    BODY.  511 

flame  and  animal  life  are  extinguished,  owing  to  lack  of  oxygen.  It  acts  as 
a  diluent  of  atmospheric  oxygen,  thereby  retarding  combustion,  but  on  higher 
animal  life  it  is  certainly  without  direct  influence. 

Ammonia,  NH3,  is  found  in  the  atmosphere  as  nitrate  and  nitrite  to  the 
extent  of  one  part  in  one  million.  It  is  found  in  the  urine  in  small  quantities, 
is  a  constant  product  of  the  putrefaction  of  animal  matter,  and  is  a  product  of 
trypsin  proteolysis. 

Preparation. — (1)  Through  the  action  of  nascent  hydrogen  on  nascent 
nitrogen.     This  may  be  brought  about  by  dissolving  zinc  in  nitric  acid, 

3Zn  +  6HNO3  =  3Zn(M)3)2  +  6H.     . 
10H  +  2HN03  =  6H20  +  2N. 
N  +  3H  =  NH3. 

Ammonia  is  produced  in  a  similar  way  in  the  dry  distillation  of  nitro- 
genous organic  substances  in  absence  of  oxygen,  being  therefore  a  by-product 
in  the  manufacture  of  coal-gas.  In  putrefaction  nascent  hydrogen  acts  on 
nascent  nitrogen,  producing  ammonia,  which  in  the  presence  of  oxygen  becomes 
oxidized  to  nitrate  and  nitrite,  or  in  the  presence  of  carbonic  oxide  is  con- 
verted into  ammonium  carbonate.  Ammonium  nitrite  is  likewise  formed  on 
burning  a  nitrogenous  body  in  the  air,  in  the  evaporation  of  water,  and  on  the 
discharge  of  electricity  in  moist  air, 

2N  +  2H20  =  NH4N02. 

At  the  same  time  a  small  amount  of  nitrate  is  formed  in  the  above  three 

processes, 

2N  +  2H20  +  O  =  NH4NOs. 

Hence  these  substances  find  their  way  into  every  water  and  soil,  and  furnish 
nitrogen  to  the  plant.  The  value  of  decaying  organic  matter  as  a  fertilizer  is 
likewise  obvious. 

Properties. — Ammonia  is  a  colorless  gas  of  pungent  odor.  It  readily  dis- 
solves in  water  and  in  acids,  entering  into  chemical  combination,  the  radical 
NH4  appearing  to  act  like  a  metal  with  properties  like  the  alkalies,  and  its 
salts  will  be  described  with  them.  Very  small  amounts  of  ammonia  instantly 
kill  a  nerve,  but  upon  muscular  substance  it  acts  first  as  a  stimulant,  provok- 
ing contractions:  1  part  of  ammonia  in  500  of  water  will  kill  an  amoeba,  and 
1  part  in  10,000  will  slow  and  finally  arrest  ciliary  motion.1 

Ammonia  in  the  Body. — If  it  be  agreed  with  Hoppe-Seyler  licit  normal 
decomposition  in  the  tissues  is  analogous  to  putrefaction,  then  nascent  hydrogen 
acting  on  nascent  nitrogen  in  the  cell  produces  ammonia,  which  in  the  presence 
of  carbonic  acid  becomes  ammonium  carbonate,  and  in  turn  may  be  converted 
into  urea  by  the  liver.  If  acids  (1IC1)  be  fed  to  carnivore  (dogs)  the  amount 
of  ammonia  present  in  the  urine  is  increased,  which  indicates  that  an  amount 
of  ammonia  usually  converted  into  urea  has  been  taken  for  the  neutralization 

1  Bokorny :  Pjliiyer's  Archiv,  1895,  Bd.  59,  S,  557. 


512  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

of  the  acid.1     In  a  similar  manner  acids  formed  from  decomposing  proteid 

may  be  neutralized  (see  pp.  506  and   550). 

The  ammoniacal  fermentation  of  the  urine  consists  in  the  decomposition  of  urea  into 
ammonium  carbonate  by  the  micrococcus  urince,  the  urine  becoming  alkaline. 

Compounds  of  Nitrogen  with  Oxygen. — There  are  various  oxides  of  nitrogen,  the 
higher  ones  being  powerfully  corrosive,  and  Borne  of  these  unite  with  water  to  form  acids, 
of  which  nitric  arid  I  1 1  N<  )..  is  the  strongest.  Only  nitrous  and  nitric  oxides  are  of  physi- 
ological interest. 

Nitrous  Oxide,  N20,  likewise  called  "laughing-gas,"  is  prepared  by  heating  ammo- 
nium nitrate, 

NH4NOs  =  NsO  +  2HaO. 

It  supports  ordinary  combustion  almost  as  well  as  pure  oxygen,  but  it  will  not  sustain  life. 
Mixed  with  oxygen  it  may  be  respired,  producing  a  state  of  unconsciousness  preceded  by 
hysterical  laughter. 

Nitric  Oxide,  NO,  is  prepared  by  dissolving  copper  in  nitric  acid, 
3Cu  +  8IIN03  =  3Cu(N03)2  +  4H,20  +  2NO. 

Contact  with  oxygen  converts  it  into  peroxide  of  nitrogen  (N02),  which  is  an  irritating 
irrespirable  gas  of  reddish  color.  Nitric  oxide  in  blood  first  unites  with  the  oxygen  of 
oxyhemoglobin,  forming  the  peroxide  1  NO,),  and  then  the  nitric  oxide  combines  with 
haemoglobin,  forming  a  highly  .-table  compound,  nitric-oxide  haemoglobin  (Hb-NO). 

Nitrogen  en  the  Body. — Nitrogen  is  taken  into  the  body  combined  in 
the  great  group  of  proteid  substances,  which  are  normally  completely  absorbed 
by  the  intestinal  tract.  It  passes  from  the  body  in  the  form  of  simple  decom- 
position-products, in  larger  part  through  the  urine,  but  likewise  through  the 
juices  which  pour  into  the  intestinal  canal.  The  unabsorbed  residues  of  these 
latter  juices,  mixed  with  intestinal  epithelia  constitute  in  greater  part  the  feces.2 
An  almost  insignificant  amount  of  nitrogen  is  further  lost  to  the  body  through 
the  hair,  nails,  and  epidermis,  but,  generally  speaking,  the  sum  of  the  nitrogen 
in  the  urine  and  feces  corresponds  to  the  proteid  decomposition  for  the  same 
time  (1  gram  N  =  6.25  grams  proteid).  When  the  nitrogen  of  the  proteid  eaten 
is  equal  in  quantity  to  the  sum  of  that  in  the  urine  and  feces,  the  body  is  said 
to  be  in  nitrogenous  equilibrium.  When  the  ingested  nitrogen  has  been  larger 
than  that  given  off,  proteid  has  been  added  to  the  substance  of  the  body;  when 
smaller,  proteid  has  been  lost.  These  propositions  were  established  by  Carl 
Voit. 

A  small  amount  of  urea  and  other  nitrogenous  substances  may  be  excreted  in  profuse 
sweating.  Proteid  nitrogen  never  leaves  the  body  in  the  form  of  free  nitrogen  or  of 
ammonia.  That  ammonia  is  not  given  off  by  the  lungs  may  be  demonstrated  by  perform- 
ing tracheotomy  on  a  rabbit,  and  passing  the  expired  air  first  through  pure  potassium 
hydrate  (to  absorb  CO.,]  and  then  through  Nessler's  reagent.  The  experiment  maybe 
continued  for  hours  with  negative  result.3 

1  Fr.  Walther:  Archiv  fur  exper.  Pathologie  und  Pharmakologie,  1877,  Bd.  7,  S.  164. 
1  Menichanti  and  Prausnitz :  Zeitechrifi  fur  Biologic,  1894,  Bd.  30,  S.  353. 
1  Bachl :  Zeitechrifi  fur  Biologic,  1869,  Bd.  5,  S.  61. 


THE    CHEMISTRY    OF    THE   ANIMAL    BODY.  513 

Phosphorus,  P  =-32. 

Phosphorus  is  found  combined  as  phosphate  in  the  soil ;  it  is  necessary  to 
the  development  of  plants.  As  phosphate  it  is  present  in  large  quantity  in 
the  bones,  and  is  found  also  in  all  the  cells,  tissues,  and  fluids  of  the  body, 
probably  in  loose  chemical  combination  with  the  proteid  molecule.  It  is  pres- 
ent in  nuclein,  protagon,  and  lecithin. 

Preparation. — Phosphorus  was  first  prepared  by  igniting  evaporated  urine, 
3NaH2P04  +  5C  =  3H20  +  5C0  +  2P  +  Na3P04. 

In  a  similar  way  it  may  be  obtained  by  chemical  treatment  of  bones.  The  vapors  of 
phosphorus  may  be  condensed  by  passing  them  under  water,  where  at  a  temperature  of 
44.4°  the  phosphorus  melts  and  may  be  cast  into  stieks. 

Properties. — Phosphorus  is  a  yellow,  crystalline  substance,  soluble  in  oils  and  carbon 
disulphide.  It  is  insoluble  in  water,  in  which  it  is  kept,  since  in  moist  air  it  gives  off  a 
feeble  glowing  light,  accompanied  by  white  fumes  of  phosphorous  acid  (H3PO:))  and  small 
amounts  of  ammonium  nitrate,  peroxide  of  hydrogen,  and  ozone,  to  which  latter  the 
peculiar  odor  is  ascribed.  Phosphorus  ignites  spontaneously  at  a  temperature  of  60°,  and 
this  may  be  produced  by  mere  handling,  the  resulting  burns  being  severe  and  dangerous. 
This  form  of  phosphorus  is  poisonous,  but  if  it  be  heated  to  250°  in  a  neutral  gas  (nitrogen) 
it  is  changed  into  red  phosphorus,  which  has  different  properties  and  is  not  poisonous. 

Phosphorus-poisoning. — On  injecting  phosphorus  dissolved  in  oil  into  the 
jugular  vein,  embolisms  are  produced  by  the  oil  in  the  capillaries  of  the  lungs, 
the  expired  air  contains  fumes  of  phosphorous  acid,  and  the  lungs  glow  when 
cut  out  (Magendie).  If  the  phosphorus  oil  be  injected  in  the  form  of  a  fine 
emulsion,  embolism  is  avoided,1  and  the  fine  particles  of  phosphorus  are  generally 
distributed  throughout  the  circulation.  On  autopsy  of  a  rabbit  alter  such  injec- 
tion in  the  femoral  vein,  all  the  organs  and  blood-vessels  glow  on  exposure  to 
the  air.2  If  two  portions  of  arterial  blood  be  taken,  and  one  of  them  be  mixed 
with  phosphorus  oil,  and  they  be  let  stand,  both  portions  become  venous  in  the 
same  time.3  Hence  phosphorus  in  blood,  as  in  water,  is  not  readily  oxidized. 
Persons  breathing  vapor  of  phosphorus  acquire  phosphorus-poisoning.  What 
the  direct  action  of  phosphorus  is,  is  unknown,  but  the  results  are  most  inter- 
esting. To  understand  the  results  it  maybe  supposed  that  proteid  in  decompos- 
ing in  the  body  splits  up  into  a  nitrogenous  portion,  the  nitrogen  of  w  hioh  finds 
it- exit  through  the  urine  and  feces, and  a  non-nitrogenous  portion,  which  i-  re- 
solved into  carbonic  oxide  and  water,  just  as  arc  the  sugars  ami  the  fats.  Phis 
carbonic  acid  is  given  off,  for  the  most  part,  through  the  lungs.  Now  if  a  starv- 
ing dog,  which  lives  on  his  own  flesh  and  tilt,  be  poisoned  with  phosphorus, 
the  proteid  decomposition  as  indicated  by  the  nitrogen  in  the  urine  is  largely 
increased,  while  the  amounts  of  carbonic  acid  given  oil'  and  oxygen  absorbed 
are  largely  decreased  ;  on  post-mortem  examination  the  organs  arc  found  to 
contain  excessive  quantities  of  fat.  We  have  here  presumptive  evidence  that  a 
part  of  the  proteid  molecule  usually  completely  oxidized   has  not  been  burned, 

1  L.  Hermann:  Pjlugei'i  Archiv,  1870,  Bd.  :'>,  S.  1. 

1  II.  Meyer:  Archiv  fur  exper.  Pathologic  and  Pharmakologie,  L881,  1U1.  1  1,  S.  327. 
3  Meyer,  Op.  cit.,  S.  329. 
Vol.  I.— 33 


514  AN  AM  ERIC  AX    TEXT-BOOK    OF  PHYSIOLOGY. 

l»ut  has  been  converted  into  fat.1  Similar  results  are  characteristic  of  arsenic 
and  antimony  poisoning,  and  of  yellow  atrophy  of  the  liver.  Rosenfeld  has 
recently  shown  that  much  of  the  tat  found  in  the  liver  of  a  dog  poisoned 
with  phosphorus  is  fat  transported  from  the  fat  repositories  of  the  body  (fatty 
infiltration).  The  high  proteid  metabolism,  however,  of  itself  would  indicate 
the  retention  of  an  unburned  part  of  the  proteid  molecule,  which  in  this  case 
probably  appears  as  fat  -  (fatty  degeneration,  see  p.  559).  A  parallel  case  of 
high  proteid  metabolism  is  seen  in  diabetes,  where  sugar  from  proteid  remains 
unburned. 

Compounds  of  Phosphorus  with  Oxygen. — Of  these  compounds  three 
oxides  ami  several  acids  exist,  but  only  meta-  and  orthophosphoric  acid  need 
attention  here. 

Phosphorus  Peroxide,  P205,  is  a  white  powder,  which  rapidly  absorbs 
moisture;  it  is  produced  by  burning  phosphorus  in  dry  air. 

Metaphosphoric  Acid,  HPOs,  is  said  to  occur  combined  in  nuclein. 

Preparation. — (1)  By  dissolving  P2Os  in  cold  water, 

P205  +  H20  =  2HP03. 

(2)  By  fusing  phosphoric  acid, 

H3P04  =  HP03  +  H30. 

It  is  converted  slowly  in  the  cold,  rapidly  on  heating,  into  phosphoric  acid. 
(  r\  stalline  it  forms  ordinary  glacial  phosphoric  acid.  Metaphosphoric  acid 
precipitates  proteid  from  solution,  yielding  a  body  said  to  be  pseudonuclein,3 
but  this  seems  to  be  untrue*  (see  p.  579). 

Orthophosphoric  Acid,  H3P04. — Salts  of  this  acid  constitute  all  the  in- 
organic compounds  of  phosphorus  in  the  body,  and  are  called  phosphates. 

Preparation. — (1)  By  heating  solutions  of  metaphosphoric  acid, 

HP03  +  H20  =  H3P04. 

(2)  By  treating  bone-ash  with  sulphuric  acid, 

0a  ,(P04)2  +  3H2S04  =  3CaS04  +  2H3P04. 

Properties. — On  evaporation  of  the  liquors  obtained  above,  the  acid  separates  in  color- 
less hydroscopic  crystals. 

Phosphoric  acid  forms  different  salts  according  as  one,  two,  or  three  atoms  of  hydrogen 
arc  supplanted  by  a  metal.     Thus  there  exist  primary  sodium  or  calcium  phosphates, 

Nail, PO,  and  Ca<n    >(  >' ;  the  secondary  phosphates.  Na2IIP04  and  CaHP04:  and  the 

tertiary  phosphates,  Natl'<)4  and  Ca*(P04)s.  On  account  of  their  reaction  to  litmus 
these  salts  have  been  falsely  called  acid,  neutral,  and  basic,  but  the  secondary  salts  are, 
chemically  speaking,  acid  salts. 

The  bones  contain  a  large  quantity  of  tertiary  phosphate  of  calcium  ;  the 
fluids  and  cells  of  the  body  contain  likewise  the  primary  and  secondary  phos- 

1  J.  Bauer:  Zeitschrifl  fur  Biolnrjie,  1871,  Bd.  7,  S.  63. 

2  Kay,  McDermott,  and  Ltisk  :  American  Journal  of  Physiology,  1899,  vol.  iii.  p.  139. 

3  L.  Liebermann  :   Berichte  der  deutschen  chemischen  Gesellschaft,  Bd.  22,  S.  598. 
'Salkowski:    Pfiuger's  Archiv,  1894,  Bd.  59,   S.  245;    also,   Giertz:    Zeitschrift  fitr  physiv- 

logische  Chemie,  1899,  Bd.  28,  S.  115. 


THE   CHEMISTRY   OE   THE   ANIMAL   BODY.  515 

phates,  while  to  primary  sodium  phosphate  carnivorous  urine  mainly  owes  its 
acid  reaction. 

In  speaking  of  the  ash  of  protoplasm,  Nencki 1  advocates  the  idea  of  separate 
combinations  of  the  base  and  acid  radicles  with  the  proteid  molecule,  as,  for 
example,  the  sepauate  union  of  potassium  with  proteid  and  of  phosphoric  acid 
with  proteid,  in  the  functionally  active  cell.  However  combined,  phosphoric 
acid  is  necessary  for  the  organism. 

Phosphorus  in  the  Body. — The  principal  source  of  supply  is  derived 
from  the  phosphates  of  the  alkalies  and  alkaline  earths  in  the  foods ;  it  may  be 
absorbed  in  organic  combinations  in  nuclein,  casein,  and  caseoses ;  and  it  may 
perhaps  be  absorbed  as  glycerin  phosphoric  acid,  which  is  an  intestinal  decompo- 
sition product  of  lecithin2  and  probably  also  of  protagon.  Phosphorus  leaves 
the  body  almost  entirely  in  the  form  of  inorganic  phosphate,  the  only  exception 
being  glycerin  phosphoric  acid,  which  has  been  detected  in  traces  in  the  urine. 
In  man  and  carnivora  the  soluble  primary  and  secondary  phosphates  of  the 
alkalies  are  found  in  the  urine,  together  with  much  smaller  amounts  of  the 
less  soluble  primary  and  secondary  phosphates  of  the  alkaline  earths.  There 
is  likewise,  even  during  hunger,  a  continuous  excretion  of  tertiary  phosphate 
of  calcium,  magnesium,  and  iron  in  the  intestinal  tract.  In  herbivora  the  ex- 
cretion is  normally  into  the  intestinal  tract,  and  no  phosphates  occur  in  the 
urine.  This  is  because  herbivora  eat  large  quantities  of  calcium  salts  which 
bind  the  phosphate  in  the  blood,  and  they  likewise  eat  organic  salts  of  the 
alkalies,  which  become  converted  into  carbonate  and  appear  in  the  urine  as 
acid  carbonates ;  such  a  urine  has  no  solvent  action  on  calcium  phosphate.3 
In  a  similar  manner  a  great  reduction  of  phosphate  in  the  urine  of  man  may 
be  effected  by  feeding  alkaline  citrate  and  calcium  carbonate,  the  first  to  furnish 
the  more  alkaline  reaction  to  blood  and  urine,  the  second  to  bind  the  phosphate 
in  the  blood.  The  more  alkaline  reaction  itself  is  insufficient  to  prevent  the 
appearance  of  phosphates  in  the  urine.4  On  the  other  hand,  starving  herbiv- 
ora, or  herbivora  fed  with  animal  food,  give  urines  acid  from  primary  phos- 
phate.5 In  diabetes  where  there  is  a  large  production  of  abnormal  acids 
which  tend  to  neutralize  the  blood,  there  is  a  more  acid  urine  which  contains 
an  increased  amount  of  calcium  phosphate,  and  the  excretion  of  the  same 
through  the  intestinal  wall  correspondingly  decreases.0  During  lactation  the 
amount  of  phosphate  eliminated  through  the  ordinary  channels  is  decreased, 
for  a  considerable  amount  is  used  to  form  the  milk.7 

Excreted  phosphates  may  be  originally  derived  from  the  phosphates  of  the 
bones,  or  from  phosphates  arising  from  the  oxidation  of  nuclein,  protagon,  and 
lecithin,  but  by  far  the  greater  quantity  is  derived  from  the  food,  or  from  pro- 

1  Archiv  far  exper.  Pathologie  und  Pharmakologie,  1894,  lid.  31,  S.  334. 
-  B6kay:  Zeitichrift  fur  phynologisehe  Chemie,  ls77  78,  Bd.  1,  S.  157. 

3  J.  Bertram  :  Zeitsehrift  fur  Biologie,  1878,  Bd.  14,  S.  354.  *  Op.  cit.,  S.  354. 

4  Weiske:   Ibid.,  1872,  Bd.  8,  S.  246. 

6  Gerhardt  und  Schlesinger :  Archiv  far  exper.  Pdlhohf/ie  und  Pharmakologie,  L899,  Bd.  12, 
S.  83. 

7  Paton,  Donlop,  and  Aitchison  :  Journal  of  Physiology,  70  .  xxv.  p.  212. 


516  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

tt  id  metabolism.  In  a  starving  dog,  which  feeds  on  its  own  proteid,  it  was 
found  that  a  ratio  existed  between  nitrogen  and  phosphoric  acid  in  the  urine  as 
0.4:1,  which  approximates  that  in  muscle,  i.e.  7.6:1.  On  feeding  meat  till 
nitrogenous  equilibrium  was  established,  the  ratio  became  8.1 :  l.1  On  addi- 
tion of  proteid  to  the  body,  a  proportionate  amount  of  phosphoric  acid  is  re- 
tained for  the  new  protoplasm,  while  on  destruction  of  proteid  the  phosphoric 
acid  corresponding  to  it  is  eliminated.  In  diabetes  where  the  proteid  metab- 
olism i>  far  above  the  normal,  the  phosphorus  excretion  remains  propor- 
tional to  the  proteid  destroyed.2  The  larger  excretion  of  phosphoric  acid 
during  hunger  shown  in  the  ratio  above,  has  been  ascribed  to  the  decomposi- 
tion of  the  bones.3  Thus  Munk  found  on  Cetti,  who  lived  many  days  without 
food,  a  ratio  as  low  as  4.5:1.  In  starvation  the  brain  and  nerves  do  not 
decrease  in  weight,  so  the  protagon  can  hardly  yield  any  great  amount  of  phos- 
phoric acid  (Voit).  Casein  and  other  nucleo-albumins,  when  fed,  are  oxidized 
and  furnish  phosphoric  acid  for  the  urine. 

Carbon,  C  =  12. 

This  element  is  found  combined  in  every  organism,  and  in  many  decom- 
position-products of  organized  matter.  Elementary  carbon  occurs  as  lamp- 
black, diamond,  and  graphite,  the  two  latter  having  their  origin  from  the  action 
of  high  heat  on  coal.  Carbon  occurs  combined  in  coal,  petroleum,  and  natural 
gas,  which  are  all  products  of  the  decomposition  of  wood  out  of  contact  with  the 
air.  Further  it  is  found  in  vast  masses,  principally  consisting  of  calcium  car- 
bonate, having  their  origin  from  sea-shells.  The  maintenance  of  life  depends,  as 
will  be  shown,  on  the  small  percentage  of  carbon  dioxide  which  is  contained  in  the 
atmosphere.  Lavoisier  believed  that  compounds  of  carbon  were  all  products 
of  life,  formed  under  the  influence  of  a  '"  vital  force,"  which  was  a  property 
of  the  cell.  It  is  now  known  that  almost  every  constituent  of  the  cell  may  be 
prepared  from  its  elements  in  the  laboratory  without  the  aid  of  any  "vital 
force"  whatever.  Notwithstanding  its  loss  of  strict  scientific  significance,  the 
old  term  "organic"  for  a  carbon  compound  is  still  in  vogue,  and  conveniently 
describes  a  large  number  of  bodies  which  are  treated  under  the  head  of  "or- 
ganic chemistry,"  while  the  term  "inorganic"  is  applied  to  the  rest  of  the 
chemical   world. 

Elementary  Carbon. — This  burns  only  at  a  high  heat.  It  is  unaffected 
by  the  intestinal  tract.  This  is  shown  by  the  fact  that  diamonds  have  been 
stolen  by  -wallowing  them,  and  that  finely  divided  particles  of  lampblack  pass 
unchanged  and  unabsorbed  to  the  feces,  coloring  them  black  (proof  that  the 
intestinal  canal  does  not  absorb  solid  particles).  If  lampblack  be  eaten  with  a 
meal  its  appearance  in  the  feces  may  be  used  as  a  demarcation  line  between  the 

1  E.  Bischoff:  Zeilschrift  jr,,-  Bidogie,  1867,  Bd.  3,  S.  309. 

2  Colaasanti  e  Bounani:  Boll.  <l.  II.  A'<-'t</.  med.  ili  Roma,  1896-1897;  Reilly,  Nolan,  and 
Lusk  :  American  Journal  of  Physiology,  1898,  vol.  i.  p.  395. 

3  See  Voit :  Hermann's  Handbueh,  L8S1,  vi.  1,  s.  79. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  517 

feces  belonging  to  the  period  before  the  meal,  and  the  period  subsequent  to  it. 
Carbon  unites  directly  with  hydrogen,  oxygen,  and  sulphur  only. 

Carbon  Monoxide,  CO. — This  gas  is  a  product  of  the  incomplete  combus- 
tion of  carbon,  is  present  in  illuminating  gas,  and  burns  on  ignition  to  carbon 
dioxide. 

Properties. — A  colorless,  odorless  gas.  Inspired,  it  unites  with  the  blood 
to  form  a  carbon-monoxide  haemoglobin  (Hb-CO).  This  is  a  very  stable 
bright-red  compound  which  may  even  be  boiled  without  decomposing.  Ani- 
mals poisoned  with  CO  die  from  want  of  oxygen,  since  the  latter  cannot  dis- 
place the  carbon  monoxide  from  combination  with  haemoglobin.  Carbon 
monoxide  poisoning  is  accompanied  by  diabetes1  probably  because  of  de- 
creased power  to  burn  sugar. 

Carbon  Dioxide,  C02. — This  is  the  highest  oxidation  compound  of  carbon, 
the  product  of  its  complete  combustion.  It  is  present  in  the  air  to  the  extent 
of  0.04  per  cent.  It  is  formed  in  all  living  cells,  and  in  higher  animals  is 
collected  by  the  blood  and  brought  to  the  lungs  and  skin  for  excretion  ;  it  is 
also  a  product  of  putrefaction ;  it  gives  an  acid  reaction  to  herbivorous  urine. 
It  is  found  dissolved  in  all  natural  waters,  and  is  present  combined  in  sea 
shells.  It  is  found  in  the  blood  principally  combined  with  sodium  in  the 
serum,  and  is  likewise  combined  with  calcium  and  magnesium  in  the  bones. 

Preparation. — (1)  By  burning  carbon  or  a  carbon-containing  substance, 
C6H1206  +  120  ==  6C02  +  6H20. 

Sugar. 

(2)  By  heating  a  carbonate, 

CaC03=CaO+C02. 

(3)  By  the  action  of  an  acid  on  a  carbonate, 

Na2COs  +  2HC1  —  2NaCl  +  C02  +  H20. 

In  the  blood,  haemoglobin  and,  to  a  less  extent,  serum-albumin  and  primary 
sodium  phosphate  act  like  acids.  If  the  gases  be  extracted  from  fresh  defib- 
rinated  blood  in  a  vacuum,  all  the  C02  is  removed.  If  sodium  carbonate  be 
added  to  blood,  the  carbonic  acid  belonging  to  this  is  likewise  given  up  in  a 
vacuum,  while  a  simple  aqueous  solution  of  sodium  carbonate  is  not  affected. 
If  serum  be  extracted  in  vacuo,  only  a  little  more  than  half  the  carbonic  acid 
contained  in  it  is  dissociated  from  combination,  indicating  that  in  the  previous 
experiment  haemoglobin  had  acted  like  an  acid.  If  a  solution  of  bicarbonate 
of  sodium  (NaHC03)  be  exhausted  under  the  air-pump,  just  one-half  of  the 
C02  is  given  off,  sodium  carbonate  (Na2C03)  remaining.  In  the  serum  more 
than  one-half  of  the  C02  is  obtained  in  vacuo,  because  the  serum-albumin, 
like  the  haemoglobin,  though  less  effectively,  acts  like  an  acid  in  fixing  the 
alkali  and  liberating  the  gas.  There  is  likewise  present  the  action  of  pri- 
mary phosphate  on  the  acid  carbonate, 

NaH2P04  +  NaHCO,  =  Na2HPO,  +  H20  -f  CO, 

1  Straub:  Archiv fur  experimentelle  Pathologie  wnd  Pha.rmakol»<jic,  ls'iti,  l:<].  :;s,  s.  |:><J 


518  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

Through  these  agencies  the  tension  of  carbonic  acid  is  kept  hiffh  in  the  Mood, 
and  its  escape  through  the  walls  of  the  alveolar  capillary  is  not  unlike  the 
escape  of  gas  on  uncorking  a  bottle  of  carbonated  water. 

After  drinking  a  carbonated  water,  carbonic  oxide  may  be  detected  dissolved 
in  the  urine. 

Properties. — A  colorless,  odorless  gas.  It  is  poisonous,  its  accumulation  at 
first  stimulating  and  afterwards  paralyzing  the  nervous  centres.  It  affects  the 
irritability — not,  however,  the  conducting  power — of  the  nerves.  A  solution 
of  carbonic  oxide  in  water  forms  carbonic  acid,  H2C03,  and  from  this  are  derived 
two  series  of  salts,  primary  or  acid  salts,  MHC03,  and  secondary  or  neutral 
salts,  M2C03. 

Metabolism  of  Carbon. — It  will  be  remembered  that  there  is  a  union  of 
chlorine  and  hydrogen  on  exposure  to  sunlight.  In  a  similar  manner  the  chloro- 
phvll-containing  leaf  of  the  plant,  through  the  medium  of  the  energy  of  the  sun's 
ravs,  brings  the  molecules  of  water  and  carbonic  oxide  derived  from  the  air  in 
such  a  position  with  regard  to  each  other  that  they  unite  to  form  sugar  with  the 
elimination  of  oxygen  (reaction  on  p.  501).  This  process  is  called  synthesis — 
the  construction  of  a  more  complicated  body  from  simpler  ones.  The  active  or 
"kinetic"  energy  from  the  sun  required  to  build  up  the  compound  is  stored, 
becoming  "  potential "  energy  in  that  compound,  and  is  liberated  again  in 
exactly  the  same  quantity  on  the  resolution  of  the  substance  into  its  original 
constituents.  So  the  amount  of  energy  liberated  in  the  decomposition  of  a 
food  in  the  body  is  exactly  equal  to  the  energy  needed  to  build  it  up  from 
its  excreted  constituents,1  and  this  liberated  energy  appears  in  the  body  as 
heat,  work,  and  electric  currents. 

The  plant  has  the  power  of  converting  sugar  into  starch  and  cellulose,  and 
likewise  into  fat.  Further  the  sugar  undoubtedly  unites  with  certain  nitrogen- 
containing  bodies,  and  the  synthesis  of  proteids  results.  Plants  containing  this 
mixture  of  food-stuffs  become  the  sustaining  basis  of  animal  life.  The  animal 
devours  these  substances  and  either  adds  them  to  his  body,  or  burns  them  to 
prevent  destruction  of  his  own  substance:  such  are  the  objects  of  food.  In 
contradistinction  to  synthesis  in  plants,  animal  life  is  said  to  be  characterized  by 
analysis,  i.  e.,  the  resolution  of  a  complicated  substance  into  simpler  ones.  This 
classification  is  not  entirely  accurate,  many  exceptions  occurring  on  both  sides; 
for  example,  animals  may  convert  sugar  into  fat,  which  is  synthesis.  The 
animal  discharge-  its  carbon  partly  as  carbonic  acid,  and  partly  in  the  form 
of  inure  complex  organic  compounds, such  as  urea  and  uric  acid.  Since  these 
latter  after  leaving  the  body  eventually  become  oxidized,  and  the  carbon 
becomes  completely  changed  to  carbon  dioxide,  it  follows  that  all  animal  carbon 
i-  finally  restored  to  the  air  in  the  form  of  carbon  dioxide.  Thus  is  established 
the  revolution  of  the  carbon  atom,  made  possible  by  the  energy  of  the  sun, 
between  air,  plants,  animals,  and  back  to  air  again.  Burning  coal,  lime-kilns, 
volcanoes,  give  carbonic  acid  to  the  air.  Rain  water  receive-  carbonic  acid 
from  the  atmosphere,  from  putrefying  organic  matter  in  the  soil  and  from  the 
1  See  Rubner,  Zeitschrift  fur  Biologic,  L893,  lid.  30,  S.  73. 


THE   CHEMISTRY   OF   THE  ANIMAL    BODY.  519 

roots  of  trees,  and  ultimately  much  of  this  combines  with  mineral  matter,  or 
contributes  to  form  shells  in  marine  life. 

Silicon,  Si  =  28. 

Silicon  is  found  in  the  ash  of  plants,  and  in  traces  in  the  cells  and  tissues  of 
animals,  being  a  constant  constituent  of  hen's  eggs.  It  appears  in  traces  in  the 
human  urine,  and  in  considerable  quantity  in  herbivorous  urine.  It  is  especially 
present  in  hair  and  feathers.  It  does  not  seem  to  be  of  great  importance  to  the 
life  of  the  plant,  for  if  corn-stalks,  whose  ash  usually  contains  20  per  cent,  of 
silica  (Si02),  be  grown  in  a  soil  free  from  it,  the  plant  flourishes  though  only 
0.7  per  cent,  of  silica  is  found  in  the  ash,  this  having  been  derived  from  the 
vessel  holding  the  soil. 

Silicon  Dioxide,  or  Silica,  Si02. — This  is  the  oxide  of  the  element,  and  is  found  in 
quartz  and  sand,  but  not  in  the  organism. 

Silicic  Acids. — The  ortho-silicic  acid  (H4SiOJ  is  formed  by  the  action  of  an  acid  on  a 
metallic  silicate, 

Ca.SiO*  +  2H2C03  =  2CaC03  +  H4Si04. 

This  reaction  takes  place  in  the  soil,  and  the  silicic  acid  so  obtained  is  soluble  in  water  and 
is  a  colloid — that  is  to  say,  is  of  gelatinous  consistence,  will  not  crystallize,  and  does  not 
osmose  through  vegetable  and  animal  membranes.  However,  it  is  in  this  form  or  in  the 
form  of  soluble  alkaline  silicate  that  it  is  probably  received  by  the  root  of  the  plant.1 

Metasilicic  acid  has  the  formula  H2Si03,  while  the polysilicic  acids  (H2Si05,H6Si207,  etc. ) 
are  numerous,  and  constitute  the  acid  radicals  of  most  mineral  silicates.  If  silicic  acid  be 
evaporated  and  dried,  it  leaves  a  gritty  residue  of  silica. 

The  Metallic  Elements. 
The  metals  in  the  body  are  the  alkalies  potassium  and  sodium,  the  alkaline 
earths  calcium  and  magnesium,  and  the  heavy  metal  iron. 

Potassium,  K  =  39. 

Potassium  salts  are  found  especially  in  all  animal  cells  (see  p.  499),  and  in  the 
milk  which  is  manufactured  from  the  disintegration  of  such  cells.  They  are 
found  in  the  blood-corpuscle  sometimes  to  the  almost  complete  exclusion  of  ■ 
sodium  salts.  Only  to  a  small  extent  do  they  occur  in  the  fluids  of  the  body 
and  in  the  blood  plasma  (K2O  =  0.02  per  cent,  in  plasma).  They  are  excreted 
in  the  urine.  Potassium  salts  are  retained  on  the  surface  of  the  ground  for  the 
use  of  vegetation,  and  occur  in  the  plant  not  only  as  inorganic  but  also  as 
organic  salts  (tartrate,  citrate,  etc.). 

Potassium  Chloride,  KC1. — Potassium  chloride  is  a  constant  constituent 
of  all  animal  cells  and  tissues,  and  may  be  absorbed  with  the  food  <>r  be  pro- 
duced in  the  body  after  eating  potassium  carbonate  or  phosphate,  since  these  salts 
may  react  with  the  sodium  chloride.  If  fed,  it  is  ordinarily  balanced  by  its  ex- 
cretion, but  if  0.1  gram  be  introduced  into  the  jugular  vein  of  a  medium-sized 
dog,  immediately  paralysis  of  the  heart  ensues.  It  is  a  powerful  poison  fornerves 
and  nervous  centres.  It  melts  when  heated  to  a  low  red  heat,  and  volatilizes 
at  a  higher  heat. 

1  Bunge:  Physiologixche  Chemie,  3d  ed.,   1894,  S.  25. 


520  AS    AMERICAS    TEXT-BOOK    OF   PHYSIOLOGY. 

Potassium  Phosphates. — The  primary  (K H2PG4)  and  secondary  (K2HP04) 
phosphate  of  potassium  are  the  principal  .silts  <>f  the  cells  of  the  body,  and  are 
likewise  present  in  the  urine,  and  to  a  very  small  extent  in  the  blood-plasma. 
They  are  undoubtedly  intimately  connected  with  the  functional  activity  of  proto- 
plasm. Presence  of  carbonic  acid  causes  the  conversion  of  the  secondary  phos- 
phate into  the  primary  salt,  and  this  occurs  in  the  blood-corpuscle  as  well  as  in  the 
plasma  : 

K2HP<  )4  +  C<  )2  +  H20  =  KH2P04  +  KHCO3. 

Primary  acid  phosphate  of  potassium  contributes  to  the  acid  reaction  of  the 
urine,  though  in  presence  of  .-odium  chloride  there  is  a  tendency  to  the  forma- 
tion of  primary  sodium  phosphate  and  potassium  chloride.  It  is  the  cause  of 
the  acid  reaction  in  muscle  in  rigor  mortis  (see  p.  546). 

Potassium  Carbonates. — The  primary  and  secondary  carbonates  exist 
in  the  body  only  in  trifling  quantities.  They  may  be  produced  as  above  de- 
scribed by  the  action  of  carbonic  acid  on  the  phosphates,  they  may  be  ingested 
with  the  food,  or  they  may  result  in  the  body  from  the  combustion  of  an  organic 
salt  of  potassium,  according  to  the  same  reaction  as  would  take  place  by  burn- 
ing it  in  the  laboratory, 

KAH4Ofl  +  50  =  K2COs  +  3C02  +  2H20. 

K  tartrate. 
Feeding  potassium  carbonate  or  an  organic  salt  of  potassium  makes  the  urine 
alkaline  owing  to  the  excretion  of  potassium  carbonate. 

Potassium  salts  are  poisonous  if  introduced  into  the  blood  in  too  large  quantities.  In 
concentrated  solutions  in  the  stomach  the}7  produce  gastritis,  even  with  quickly  fatal 
results.' 

Zuntz  believes  that  potassium  is  combined  with  haemoglobin  in  the  blood-corpuscle,  and 
may  be  dissociated  from  it  by  the  action  of  carbonic  oxide.2 

Potassium  in  the  Body. — The  various  salts  of  potassium  are  received 
with  the  food  in  the  manner  described  ;  the  phosphate  may  be  retained  for 
new  tissue,  but  the  other  salts  are  removed  in  the  urine.  They  are  all  quite 
completely  absorbed  in  the  intestinal  tract.  In  starvation,  or  in  fever,  where 
there  is  high  tissue-metabolism,  the  body  suffers  greater  loss  of  the  potassium 
phosphate-containing  tissue  than  it  does  of  the  sodium-rich  blood,  and  potas- 
sium exceeds  sodium  in  the  urine  (reverse  of  the  usual  proportion);  also 
milk,  which  is  prepared  from  tissue,  contains  more  potassium  than  sodium. 
Bunge3  has  noted  an  important  influence  of  potassium  salts.  If  a  potassium 
sail  be  in  solution  together  with  .-odium  chloride,  the  two  partially  react  on 
each  other,  with  formation  of  potassium  chloride.  If  now  potassium  carbon- 
ate, for  example,  be  eaten,  the  same  reaction  occurs  in  the  body, 

K2(  !< >,  +  2Na<  11  =  2KC1  +  Na2C03. 

The  kidney  has  the  power  of  removing  soluble  substances  which  do  not  belong 
to  the  blood  or  are  present  in  it  to  excess,  and  consequently  the  two  salts 

1  Bunge:   Physiologiache  CKemie,  3d  ed.,  1894,  S.  136. 

s  A.  Loewy  und  X.  Zuntz:   Pfluger'i  ArcMv,  1894,  Bd.  58,  S.  522.  :;  Op.  cit.,  S.  108. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  521 

formed  as  above  are  excreted.  Hence  potassium  carbonate  has  caused  a  direct 
loss  of  sodium  and  chlorine.  For  this  reason,  if  potatoes  and  vegetables  very 
rich  in  potassium  salts  are  eaten,  sodium  chloride  must  be  added  to  the  food  to 
compensate  for  the  loss.  Nations  living  on  rice  do  not  need  salt,  for  here  the 
potassium  content  is  low.  Tribes  living  solely  on  meat  or  fish  do  not  use 
salt,  but  care  is  taken  that  the  animals  slaughtered  for  food  shall  not  lose  the 
blood,  rich  in  sodium  salts,  and  strips  of  meat  dipped  in  blood  are,  by  some 
races,  considered  a  delicacy.1 

Sodium,  Na  =  23. 

Sodium  salts  belong  particularly  to  the  fluids  of  the  body  (see  p.  504), 
blood-plasma  containing  0.4  per  cent,  calculated  to  Na2<  >. 

Sodium  chloride,  NaCl,  is  found  in  all  the  fluids  of  the  body.  It  is  found 
in  blood  and  lymph  to  an  extent  of  about  0.65  per  cent.,  in  the  saliva,  gastric 
juice,  milk,  sweat,  urine,  etc.  Sodium  chloride,  like  potassium  chloride,  melts 
at  a  low  red  heat,  hence  the  fluids  of  the  body  yield  a  fluid  ash,  with  the  single 
exception  of  milk,  which  contains  a  high  percentage  of  infusible  calcium  phos- 
phate. Sodium  chloride  is  very  readily  soluble.  In  the  blood  it  acts  as  a 
solvent  on  serum-globulin  and  other  proteids,  and  its  inert  presence  in  proper 
concentration  affords  a  medium  in  which  the  functional  activity  of  cells  and 
tissues  is  maintained.  (For  "physiological  salt-solution"  see  p.  504.)  From 
sodium  chloride  the  hydrochloric  acid  of  the  gastric  juice  is  prepared  (sec  p. 
508) ;  it  is  also  a  necessary  addition  to  every  food  where  potassium  salts  are 
in  great  preponderance  (see  p.  520),  but  it  is  taken  by  most  races  in  amounts 
far  above  these  physiological  necessities. 

If  a  mixture  of  necessary  food-stuffs — proteid,  fats,  starch,  salts,  and  water — in  proper 
proportion,  but  without  flavor,  be  set  before  a  dog,  he  will  starve  rather  than  touch  it.  A 
man  will  attempt  its  digestion,  but  the  permanent  support  of  life  is  impossible.  A  food 
to  support  life  must  be  a  well-tasting  mixture  of  food-stuffs,  lor.  through  the  action  of  the 
flavor  on  the  mucous  membrane  of  the  mouth  and  stomach  there  is  established  reflexly  a 
nervous  influence  causing  a  proper  flow  of  the  various  digestive  juices.  Hence  salt, 
pepper,  mustard,  beer,  wine,  and  other  condiments  are  taken  with  the  food.  What  the 
change  is,  when  a  substance  acts  on  the  taste-buds  of  the  tongue,  for  example,  start- 
ing a  motion  such  as  is  afterwards  interpreted  in  the  brain  as  flavor,  is  unknown. 
Chemical  constitution  gives  no  hint  how  a  body  will  taste  or  smell. 

In  carnivora  every  trace  of  sodium  chloride  is  absorbed  by  the  villi  from 
the  intestinal  tract.  This  is  a  proof  that  absorption  does  not  depend  on  simple 
physical  osmosis,  in  which  case  the  intestinal  contents  would  tend  to  have  the 
same  percentage  composition  as  the  blood,  but  upon  the  selective  capacity  of  the 
exposed  protoplasm  of  the  villi.  Sodium  chloride  is  the  principal  solid  con- 
stituent of  sweat  and  of  tears.  Usually,  however,  it  is  lost  to  the  body 
through  the  urine,  of  whose  ash  it  forms  the  chief  constituent.  The  quantity 
of  salt  in  the  urine  is  decreased  during  gastric  digestion  (sec  p.  508).  Sodium 
chloride  if  fed  is  largely  excreted  in  the  urine  within  the  following  twenty- 
four  hours.2     Experiments  of  abstention  from  .-ah    have  aever  been  carried 

1  I'.unge:   Op.  cit.,  S.  116.  'Strajib:  Zeitschrift fur  Biologie,  1899,  Bd.  37,S.  483. 


522  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

so  far  as  to  produce  vital  disturbances,  but  the  physiological  minimum  is 
probably  very  low.  A  dog  weighing  35  kilograms  may  live  on  0.6  gram  of 
salt  daily.1  Sodium  chloride,  f'c<h  produces  of  itself  alone  an  increase  of 
water  in  the  urine.  If  sodium  chloride  or  other  salts  act  as  diuretics  and 
remove  water  from  the  tissues,  an  increase  in  proteid  metabolism  results. 
Simple  withdrawal  of  part  of  the  water  from  the  tissues  raises  the  proteid 
metabolism   but    does   not   affect   the  amount    of  fat    burned.2 

Sodium  sulphate,  Xa_,S(  )4,  called  "  Glauber's  salt,"  is  found  together  with 
potassium  sulphate  in  the  urine  in  the  condition  of  preformed  sulphuric  acid 
(see  p.  507).  If  fed,  it  reappears  in  the  urine.  It  acts  on  the  epithelial  cells 
of  the  intestines,  preventing  the  absorption  of  water,  consequently  causing  diar- 
rhoea.    Other  laxatives  act  in  the  same  way. 

Sodium  Phosphates. — The  primary  (NaH2P04)  and  the  secondary 
(Xa.,HP04)  salts  are  found  to  a  small  extent  iu  the  blood-plasma  and  other 
Huids,  and  in  the  urine.  As  with  the  potassium  phosphates,  carbonic  oxide 
acts  when  in  certain  excess  to  convert  the  secondary  phosphate  into  NaH,P04 
and  XaIIC03.  These  two,  however,  may  react  on  one  another  to  drive  off  car- 
bonic acid  (seep.  517).  Carnivorous  urine  owes  its  acid  reaction  principally 
to  primary  sodium  phosphate.  If  a  mixture  of  NaH2P04  and  Na2HP04  be 
permitted  to  diffuse  through  membranes,  the  NaH2P04  passes  through  in 
greater  quantity,  and  this  process  may  take  place  in  the  kidney.3  Secondary 
sodium  phosphate  dissolves  uric  acid  on  warming,  forming  sodium  acid  urate 
and  primary  phosphate,  which  solution  reacts  acid  (Voit).  Urine  standing  in 
the  cold  precipitates  uric  acid  with  the  formation  of  secondary  phosphates, 
while  the  reverse  reaction  with  return  of  original  acidity  takes  place  on  warm- 
ing the  urine. 

Sodium  Carbonates. — Of  these  there  are  two,  the  primary,  NaHC03,  and 
the  neutral,  XaX  '( )...  The  organism  owes  its  alkaline  reaction,  and  also  its 
power  of  combining  with  carbonic  acid,  almost  entirely  to  sodium  carbonate. 
Saliva,  pancreatic  and  intestinal  juice  arc  strongly  alkaline  with  sodium  carbon- 
ate, as  are  also  blood,  lymph,  and  other  Huids.  If  the  organism  be  acidified,  by 
feeding  acid  to  a  rabbit,  for  example,  death  occurs  even  before  complete  loss 
of  the  blood'-  alkalinity,  while  venous  injections  of  sodium  carbonate  at  the 
proper  time  restore  the  animal.  Carbonic  oxide  cannot  be  removed  from  the 
ti—ues  in  the  acidified  blood.  Sodium  carbonate  treated  with  carbonic  acid 
becomes  acid  sodium  carbonate,  and  this  change;  is  effected  in  the  internal  res- 
piration, where  the  cells  give  C02  to  the  blood.  Treated  with  acids,  both  car- 
bonates liberate  carbonic  oxide — a  reaction  which  takes  place  in  the  blood 
(see  p.  517).  Bunge  suggests  that  the  acid  chyme  of  the  stomach,  into  whose 
finest  particle-  the  alkaline  intestinal  juice' diffuses,  i-  especially  penetrable  by 
the  hitter's  enzymes,  because  liberated  carbonic  oxide  has  separated  the  particles 
of  chyme  from  each  other.  The  same  principle  would  hold  true  of  a  morsel 
well  mixed  with   saliva,  which,  as  is  well  known,  is  more  easily  penetrable  by 

1  Voit:   ]!■  rniiiiin'x  Iltimllnirh,  18S1,  vi.  1,  S.  307. 

*Straub:  ZeiUchriflfiir  Biologk,  1899,  Bd.  38,  S.  537. 

3  Soubiranski  :  Archiv  fiir  expqr.  Pathologu  und  Pharmakologie,  1895,  Bd.  35,  S.  178. 


THE   CHEMISTRY  OF  THE  ANIMAL   BODY.  523 

gastric  juice  than  one  not  so  mixed.  Sodium  carbonate  may  be  obtained  for 
the  body  either  directly  from  the  food  by  absorption,  or  indirectly  through 
combustion  of  sodium  organic  salts.  Ingested  in  sufficiently  large  quantities, 
it  makes  the  urine  alkaline. 

Sodium  salts  are  undoubtedly  united  with  serum-albumin  in  the  plasma, 
forming  a  combination  which  may  be  dissociated  by  carbonic  oxide. 

Sodium  gives  a  yellow  coloration  to  a  colorless  flame,  and  a  distinctive  bright  line  in  the 
yellow  of  the  spectroscope. 

Sodium  in  the  Body. — This  subject  has  been  discussed  under  the  different  salts,  and 
likewise  under  potassium  and  hydrochloric  acid ;  repetition  here  is  therefore  needless. 

Ammonium,  NH4. 

Ammonia,  NH3,  has  already  been  described  (p.  511). 

Sodium-Ammonium  Phosphate,  NaNH4HP04,  is  an  insoluble  salt  formed  in  the 
urine  during  ammoniacal  fermentation. 

Ammonium  Carbonate,  (NH4)2C03,  is  formed  by  the  union  of  carbonic 
oxide  and  ammonia  in  the  presence  of  water,  and  is  therefore  a  usual  product 
of  putrefaction.  If  introduced  into  the  blood,  it  is  converted  into  urea  by  the 
liver.  In  uremia  urea  passes  from  the  blood  into  the  stomach  and  is  there 
converted  into  ammonium  carbonate,  which  produces  vomiting  through  irrita- 
tion of  the  mucous  membrane.  (See  further  discussion  under  Carbamic  Acid 
and  Urea.) 

Calcium,  Ca  =  40. 

Calcium  is  by  far  the  most  abundant  metallic  element  in  the  body,  and,  as 
has  been  found  in  the  dog,  99.5  per  cent,  belongs  to  the  composition  of  the 
bones.1  Outside  the  bones  it  occurs  most  abundantly  in  blood-plasma.  It  is 
found  in  all  the  cells  and  fluids  of  the  body,  probably  loosely  combined  with 
proteid.     Calcium  is  always  accompanied  by  magnesium. 

Calcium  Chloride,  CaCl2,  is  found  in  small  quantities  in  the  bones. 

Calcium  Fluoride,  CaF2,  a  salt  insoluble  in  water,  is  found  in  bone,  den- 
tine, and  enamel  (see  p.  510). 

Calcium  Sulphate,  CaS04,  is  found  in  small  quantities  in  bones  and  rarely 
as  part  of  the  sediment  in  strongly  acid  urine. 

Calcium  Phosphates. — Of  these  there  are  three — primary,  CaH4(P04)2, 
secondary,  CaHP04,  and  tertiary,  Ca3(P04)2.  The  tertiary  phosphate  is  insol- 
uble in  water,  the  secondary  only  very  slightly  soluble,  but  the  primary  salt  is 
soluble.  The  tertiary  and  secondary  phosphates  are  insoluble  in  alkali,  but 
soluble  in  mineral  acids  and  in  acetic  acid.  The  tertiary  phosphate  forms  the 
largest  mineral  constituent  of  the  bones  (83.89  per  cent.,  Zalesky)  and  of  den- 
tine and  enamel.  Tertiary  phosphate  of  calcium  likewise  occurs  in  the  blood; 
how  it  is  held  in  solution  it  is  difficult  to  say,  though  it  is  probably  loosely 
combined  with  proteid.  In  a  similar  way  it  is  combined  with  the  protoplasm 
of  the  cell.  It  is  largely  found  in  the  ash  of  milk,  having  been  in  previous 
chemical  combination  with  casein.  Tertiary  phosphate  of  calcium  is  continu- 
1  Ileiss:  Zeitschriftfiir  Biologie,  1876,  Bd.  12,  S.  165. 


524  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

ously  excreted  into  the  intestinal  tract.    It  is  present  in  the  acid  gastric  juice, 

bill  only  in  traces  in  the  alkaline  saliva,  pancreatic  jnice,  and  in  the  nearly 
neutral  bile.  Tertiary  phosphates  never  occur  in  the  urine,  except  as  a  sedi- 
ment after  the  urine  has  attained  an  alkaline  reaction,  being  formed  from  the 
acid  phosphates.  In  carnivorous  urine  the  calcium  present  occurs  as  primary 
and  secondary  phosphate,  the  solution  of  the  latter  being  aided  by  the  primary 
alkali  phosphate  and  sodium  chloride.  Occasionally  a  coat  is  noticed  on  the 
surface  of  the  urine,  an  appearance  once  thought  to  be  a  sign  of  pregnancy. 
This  coat  i-  now  known  to  consist  chiefly  of  secondary  phosphate  of  calcium, 
which  may  crystallize  out  on  the  urine  becoming  alkaline.  Calcium  does  not 
occur  as  phosphate  in  an  alkaline  urine  (see  p.  515). 

Calcium  Carbonates. — Of  these  there  are  two,  the  primary  or  acid, 
CaH2(COs)2,  and  the  secondary  or  neutral  carbonate,  CaC03.  Neutral  calcium 
carbonate  is  the  substance  of  which  sea  shells,  coral,  egg-shell,  and  otoliths 
consist.  It  is  found  in  the  ash  of  bones  to  the  extent  of  13.032  per  cent. 
(Zalesky).  Apatite  is  a  mineral  having  the  formula  Ca10F2^PO4)6,  and  Hoppe- 
Seyler,  using  Zalesky's  figures,  believes  that  bone  has  a  composition  repre- 
sented by  Ca10CO3(Pb4)6,  or  3Ca3(P04)2,CaC03,  in  which  COa  has  the  position 
of  F0  in  apatite.  In  the  wasting  of  the  mineral  matter  of  bones  in  osteoma- 
hh-'m  this  formula  of  composition  remains  constant,1  one  molecule  of  calcium 
carbonate  always  being  removed  for  every  three  molecules  of  the  phosphate. 
Neutral  calcium  carbonate  is  insoluble  in  water  or  alkali,  but  dissolves  in 
water  containing  carbonic  oxide  to  form  the  soluble  acid  carbonate,  CaH2(C03)2. 
This  is  found  in  blood  and  lymph,  and  in  minute  quantities  in  all  the  tissues. 
It  is  found  in  herbivorous  urine,  which  contains  carbonic  acid  in  excess,  but  it 
i-  soon  deposited  as  neutral  carbonate  as  the  carbonic  oxide  diffuses  into  the 
air.  It  occurs  in  all  alkaline  and  neutral  urines,  though  to  a  less  extent  than 
calcium  phosphate  in  acid  urines.  It  is  found  in  pancreatic  juice  and  in  the 
saliva,  from  which  latter  is  derived  the  calcic  carbonate  which,  mixed  with 
bacteria  and  other  organic  matter,  is  deposited  as  tartar  on  the  teeth. 

The  ferment  rennet  does  not  act  in  the  absence  of  calcium  salts.  The 
coagulation  of  the  blood  requires  the  presence  of  calcium  salts.2  If  ten  parts 
of  Mood  be  drawn  into  one  part  of  a  1  per  cent,  solution  of  potassium  oxa- 
late, thus  precipitating  the  calcium,  no  coagulation  takes  place,  but  on  the 
addition  of  calcium  chloride  a  typical  fibrin  forms.  According  to  Ilammar- 
sten,3  calcium  is  only  necessary  in  the  formation  of  the  ferment.  He  lias 
prepared  fibrin  containing  only  a  trace  (0.007  per  cent.)  of  calcium.  A  solu- 
tion of  sodium  oxalate  passed  through  a  beating  excised  heart  causes  it  to 
cease  beating,'  and  nerves  and  muscles  lose  their  irritability  when  calcium 
salts  are  abstracted  from  them  with  sodium  oxalate/'     These  facts  illustrate 

1  M.  Levy:  Zeilschrift fur phyziologische  Chnnie,  1894,  Bd.  19,  S.  239. 

2  Arthus  et  Paget:  Archives  <l>>  Physiologie,  1890,  p.  739. 

5  Hamtnarsten  :  Zetiachrifl  fur  physiologische  Chemie,  1899,  Bd.  28,  S.  90. 

4  Bowel!  and  Cooke:  Journal  of  Phi/xiology,  1893,  vol.  14,  p.  219,  note. 

5  Howell  :  Ibid.,  1894,  vol.  16,  p.  47<:. 


THE   CHEMISTRY   OF   THE   ANIMAL   BODY.  525 

the  intimate  relation  between  calcium  salts  and  the  functional  activity  of 
protoplasm.  Howell1  believes  that  calcium  salts  furnish  the  primary  stim- 
ulus for  the  contraction  of  the  heart. 

Calcium  in  the  Body. — Calcium  salts  are  especially  needed  in  childhood  for  the 
growth  of  the  bones.  It  has  been  estimated  that  the  human  suckling  requires  0.32  gram 
CaO  daily,  and  in  the  milk  for  that  time  is  contained  0.55  gram  to  2.37  grams,  so  that 
there  may  easily  be  lack  of  CaO  when  absorption  is  unfavorable.  In  children  with  rickets 
the  bones  contain  too  little  calcium,  and  are  abnormally  weak  and  flexible.  This  same  con- 
dition maybe  reproduced  in  young  growing  dogs  by  feeding  them  entirely  on  meat  and  fat, 
which  contain  too  little  calcium  for  proper  skeletal  development.2  Such  dogs  grow  rapidly 
in  size,  especially  around  the  thorax,  while  the  pelvis  remains  ludicrously  small,  the  extrem- 
ities become  bent  and  finally  incapable  of  supporting  the  weight  of  the  body.  A  puppy 
of  the  same  litter  fed  on  the  same  food  but  with  the  addition  of  bones  grows  normally.  In 
certain  cases  even  when  children  are  fed  with  sufficient  calcium  they  still  have  the  rickets. 
This  might  be  due  to  a  lack  of  ability  to  absorb  the  salts,  but  this  Riidel3  has  disproved. 
To  a  child  having  rickets  he  administered  a  calcium  salt,  and  confirmed  its  absorption 
by  the  increase  in  the  calcium  contents  of  the  urine,  the  result  being  the  same  as  with 
a  normal  child.  (Example:  Normal  day,  0.0196  gram  CaO  in  urine;  after  feeding 
1.4  grams  CaO  dissolved  in  acetic  acid  the  amount  in  the  urine  rises  to  0.0396  gram  for 
the  twenty-four  hours. )  Riidel  therefore  concludes  that  the  cause  of  rickets  may  be  in  a 
local  change  of  the  bones  themselves,  whereby  calcium  salts  are  not  deposited  in  the  normal 
manner. 

In  osteomalacia  there  occurs  a  solution  of  the  salts  of  the  bones  in  adult  life,  called 
softening  of  the  bones.  In  osteoporosis,  which  is  a  simple  atrophy  of  the  bones,  similar 
effects  are  produced.  Voit*  fed  a  pigeon  for  a  year  on  washed  wheat  and  distilled  water. 
at  the  end  of  which  time  the  pigeon  apparently  did  not  differ  from  the  normal  bird.  A 
few  months  later  a  wing  was  broken,  and  the  autopsy  discovered  osteoporosis  in  high 
degree,  the  skull  being  especially  attacked.  Weiske5  has  shown  that  rabbits  ultimately 
die  when  fed  on  oats  which  are  poor  in  calcium ;  the  oats  yield  an  acid  ash  and  produce  an 
acid  urine.  On  autopsy  osteoporosis  is  found.  This  does  not  take  place  when  calcium 
carbonate  is  added  to  the  food.  Whether  the  loss  of  salts  to  the  bone  is  due  ton  normal 
metabolism,  or  to  solution  due  to  the  production  of  acids  in  the  metabolism  of  proteid, 
is  an  unanswered  problem  (see  pp.  506,  511)  the  discussion  of  which  lack  of  space  forbids.6 
In  such  experiments  as  the  above,  the  percentage  of  ash  is  always  diminished,  while  the 
percentage  of  organic  matter  always  rises,  whereas  the  actual  percentage  composition  of  the 
ash  itself  remains  the  same.  This  is  a  strong  argument  in  favor  of  the  view  that  bone  is 
a  mineral  of  definite  chemical  composition.  The  mineral  matter  of  bone  is  believed  by 
some  to  be  loosely  combined  with  the  organic  material,  principally  ossein,  but  of  this  there 
is  no  proof. 

The  exact  amount  of  calcium  salt  necessary  to  keep  up  the  supply  in  the  adult  body  is 
unknown,  but  it  must  be  exceedingly  small.  A  dog  of  3.8  kilograms  eating  with  his  food 
0.043  gram  CaO  maintains  his  calcium  equilibrium  (Heiss). 

Regarding  the  absorption  of  calcium  salts,  it  has  long  been  questioned 
whether    inorganic  salts   can    lie   absorbed,    since,  it    was   argued,    insoluble 

1  American  .four/nil  of  Physiology,  1898,  vol.  '_',  p.   17. 

2  E.  Voit :  ZeiUchriftfSr  Biologie,  18S0,  Bd.  16,  S.  70. 

3  Archiv  fur  exper.  Pathologie  und  Pharmakologie  1893,  Bd.  33,  S.  90. 
1  Hermann's  Handbueh,  1881,  vi.  1,  8.  379. 

•  Zeitschriftfur  Biologie,  1894,  Bd.  31,  8.  421. 

6  See  Weiske,  Loc.cit.;  Bunge,  Physiologische  Chemie,  :!<1  ed.,  1894,  S.  104;  V.  Noorden,  Path- 
ologie der  Stoffweehsels,  1893,  S.  48  and  413. 


526  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

phosphate  would  immediately  be  precipitated  in  the  blood.  It  has,  however, 
been  conclusively  shown  that  such  salts  when  eaten  produce  an  increase  in  the 
calcium  of  the  urine  '  and  it  is  known  that  blood  has  a  special  capability  for 
carrying  calcium  phosphate.  Calcium  carbonate  and  chloride  are  capable  of 
absorption,  while  absorption  of  the  phosphate  may  be  considered  as  still  in 
doubt.  If  calcium  chloride  be  given,  a  little  of  the  calcium  appears  in  the 
nine,  and  all  of  the  chlorine,  this  being  due  to  the  conversion  in  the  intes- 
tine of  calcium  chloride  into  calcium  carbonate  and  sodium  chloride,  which 
latter  is  completely  absorbed.  Organic  salts  of  calcium  such  as  the  acetate  are 
absorbable,  as  are  probably  proteid  combinations  with  calcium  such  as  casein. 
Milk  and  egg-yolk  are  the  foods  richest  in  calcium  salts,  cow's  milk  containing 
more  calcium  to  the  liter  than  does  lime-water.2 

The  excretion  of  calcium  takes  place  in  major  part  as  triple  phosphate  from 
the  wall  of  the  small  intestine,8  in  minor  part  through  the  urine  (for  the  latter 
see  pp.  515  and  524).  It  is  excreted  during  starvation,  and  is  the  principal 
inorganic  constituent  of  starvation  feces  (Yoit).  The  secretions  of  the  intes- 
tines,  according  to  Fr.  Miiller,4  hardly  contain  enough  calcium  to  account  for 
that  found  in  the  feces,  so  that  it  is  probably  excreted  by  the  epithelial  cells 
of  the  villus.  In  starvation  the  source  of  excreted  calcium  is  principally 
from  the  breaking  down  of  tissue,  but  partially  from  the  metabolism  of  the 
bones.  The  excretion  is  never  large.  On  subcutaneous  injection  of  small 
amounts  of  calcium  acetate  in  dogs,5  the  calcium  excretion  may  be  raised  for 
several  days.  On  venous  injection  of  0.8  gram  CaO  as  acetate,  after  one 
hour  but  0.3  gram  could  be  found  above  the  normal  in  the  blood,  and  analy- 
sis of  the  liver,  kidney,  spleen,  and  intestinal  wall  failed  to  reveal  more  than 
the  usual  minimal  amounts  of  calcium.  As  it  is  never  rapidly  excreted,  it 
must  have  been  temporarily  deposited  in  some  unknown  part  of  the  body. 

Strontium,  Sr  =  87.5. 

Cremer6  has  shown,  on  adding  strontium  phosphate  to  almost  calcium-free  food  of  young 
growing  dogs,  that  the  strontium  line  could  he  detected  in  the  suhsequent  spectral  analysis 
of  their  bones.  Weiske,7  on  feeding  young  rabbits  with  food  nearly  free  from  calcium, 
and  with  addition  of  strontium  carbonate,  found  the  ash  in  some  of  the  bones  to  contain, 
in  the  place  of  CaO,  as  high  as  4.09  per  cent,  of  SrO.  In  both  of  the  above  experiments 
the  skeleton  remained  very  undeveloped  in  comparison  with  the  normal,  so  that  strontium 
cannot  be  considered  a  physiological  substitute  for  calcium. 

1  Riidel,  Op.  cil.,  S.  79. 

2  Bunge:   I'liy.siologische  Chemie,  3d  ed.,  1894,  8.  101. 

3  Voit  F.  :  Zeitachriftfur  Biologie,  1893,  Bd.  29,  S.  325. 

4  Zeitschrift  fur  Biologie,  1894,  Bd.  20,  S.  356. 

5  Rev :  Archiv  fiir  exper,  Pathologie  unci  Pfiarmakologie,  1895,  Bd.  35,  S.  298. 

r'  SUzungtiberichte  der  Gesellschaft  fiir  Morphologic  unci  Physiologie  in  M'dnchen,  1891,  Bd.  7, 
s.  124. 

7  Zcitxrhrift  fiir  Biologie,  1894,  Bd.  31,  S.  437. 


THE   CHEMISTRY   OF   THE   ANIMAL   BODY.  527 

Magnesium,  Mg  =  24.3. 

This  is  the  second  in  importance  of  the  alkaline  earths.  It  is  present 
wherever  calcium  is  found,  but  in  comparison  with  calcium  it  has  been  little 
investigated.  It  occurs  principally  as  phosphate,  but  is  found  as  carbonate 
in  herbivorous  urine.  Of  the  total  quantity  of  magnesium  in  the  dog,  Heiss 
found  that  71  per  cent,  belonged  to  the  bones.  It  is  found  decidedly  pre- 
dominating over  calcium  in  muscle,  but  is  less  in  quantity  than  calcium  in 
the  blood. 

Magnesium  Phosphates. — Magnesium  tertiary  phosphate,  Mg3(P04)2,  is 
found  in  the  ash  of  bones  to  the  extent  of  about  1  per  cent.,  is  present  in  blood 
and  especially  in  muscle,  probably  in  combination  with  protcid,  and  contrib- 
utes to  the  functional  activity  of  protoplasm.  It  is  continuously  excreted 
by  the  walls  of  the  intestinal  canal.  The  primary  and  secondary  phosphates 
of  magnesium  are  found  in  carnivorous  urine,  solution  of  the  latter  being 
aided  by  the  presence  of  primary  alkali  phosphate  and  sodium  chloride. 
Tertiary  phosphate  of  magnesium  is  insoluble  in  water,  the  secondary  very 
slightly  so,  the  primary  quite  soluble ;  but  all  are  soluble  in  acids.  In  the  am- 
moniacal  fermentation  of  the  urine,  ammonium  magnesium  phosphate,  MgNH4- 
P04,  is  precipitated  as  a  fine  crystalline  powder  insoluble  in  alkalies.  When- 
ever this  fermentation  takes  place,  whether  in  the  bladder  or,  by  similar 
reaction,  in  the  intestines  (herbivora  especially),  stones  are  formed.1 

Magnesium  Carbonates. — The  neutral  carbonate,  MgC03,  is  insoluble  in 
water,  but  soluble  in  water  containing  carbonic  oxide,  forming  secondary  or  acid 
carbonate,  MgH2(C03)2.     This  latter  occurs  in  herbivorous  urine. 

Magnesium  in  the  Body. — Considerations  regarding  the  absorption  of 
calcium  apply  likewise  to  magnesium.  It  is  absorbed  by  the  iutestine  as  inor- 
ganic and  probably  as  organic  combinations.  If  growing  rabbits  be  fed  on 
a  diet  poor  in  calcium  salts,  but  containing  magnesium  carbonate,  the  bones 
may  be  brought  to  contain  double  the  normal  quantity  of  magnesium,  but  the 
skeletal  development  remains  far  behind  that  of  a  normal  rabbit,  and  there- 
fore  magnesium  can  in  no  sense  be  considered  a  substitute  for  calcium.2  The 
magnesium  salts,  whether  phosphate  or  carbonate,  being  more  soluble  than  the 
calcium  salts,  occur  in  the  urine  in  greater  abundance.  Indeed,  in  carniv- 
orous urine  the  major  part  of  excreted  magnesium  is  found  in  the  urine,  the 
balance  being  given  off  through  the  intestinal  wall  to  the  feces.  In  starvation 
the  source  of  the  excreted  magnesium  is  from  the  bones,  and  especially  from 
destruction  of  its  combination  in  proteid  metabolism. 

Iron,  Fe  =  56. 

This  is  the  one  heavy  metal  which  is  an  absolute  necessity  for  the  organ- 
ism. About  three  grams  occur  in  the  average  man.  It  has  been  demon- 
strated of  certain   bacteria  that  they  will  not  develop  in  the  absence  of  iron, 

1  For  example  in  man  see  C.  Th,  Mdrner:  Zeitschrift  fw  ]>hysiologische  Chemie,  1897,  Bd. 
22,  S.  522. 

2  Weiske  :  Zeitschrift  fur  Biologie,  1894,  Bd.  31,  S  437. 


528  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

and  this  is  believed  to  be  true  of  all  protoplasm.  Iron  is  found  through- 
out the  body,  and  is  especially  an  ingredient  of  haemoglobin  (0.4  per  cent.), 
which  carries  oxygen  to  the  tissues.  It  is  found  deposited  in  the  liver  and 
the  spleen  as  fcrratin.  hepatin,  and  other  less  investigated  organic  compounds. 
It  is  found  in  muscle  washed  free  from  blood.  Iron  appears  in  urine  and  in 
milk  as  organic  compounds,  and  in  the  bile,  gastric  juice,  and  intestines  as 
phosphate,  in  the  feces  as  sulphide.  Iron  occurs  in  two  forms,  the  ferro-  and 
ferri-  compounds,  in  which  it  has  respectively  two  and  three  bonds. 

Ferrosulphide,  FeS. — This  is  found  in  the  feces  and  is  the  product  of 
the  action  of  sulphuretted  hydrogen  or  alkaline  sulphide  on  both  inorganic 
iron  and  likewise,  more  slowly,  on  organic  iron-containing  compounds  (fer- 
ratin,  luematogen,  etc.).  Ammonium  sulphide  acts  in  a  similar  manner,  and, 
in  all  cases,  ferric  salts  arc  reduced  to  ferrous: 

2FeCl3  +  3(NH4)2S  =  2FeS  +  6NH4C1  +  S. 

Ferric  chloride. 

Ferric  Phosphate,  FeP()4. — This  is  found  in  the  gastric  juice,  bile,  and 
probably  in  the  intestinal  juice;1  it  is  not,  as  many  have  believed,  given  off* 
by  the  epithelia  of  the  intestines.  It  is  soluble  in  mineral  acids,  but  insoluble 
in  water,  alkalies,  or  acetic  acid. 

Ikon  ix  the  Body. — The  amount  of  iron  in  the  urine  is  very  small, 
amounting  daily  in  a  large  starving  dog  to  0.0013-0.0049  gram.5  Feeding 
iron  compounds  does  not  increase  the  amount  of  iron  in  the  urine.  Forster3 
led  a  dog  of  26  kilograms  for  thirty-eight  days  with  washed  meat  containing 
0.93  grams  of  iron,  and  in  the  feces  were  found  3.59  grams  belonging  to  the 
same  period.  Here  there  was  a  loss  of  2.66  grams4  of  iron  from  the  body, 
and  the  necessity  of  iron  as  a  food  was  established. 

Concerning  the  method  ami  the  amount  of  iron-absorption,  considerable  difficulty  has 
been  encountered  owing  to  the  fact  that  both  absorptive  and  secretive  organs  lie  in  the 
intestinal  canal.  <  hi  feeding  a  dog  for  thirteen  days  with  meat  containing  0.  Isu  gram  Fe, 
there  were  found  in  urine  and  feces  for  the  same  time  0.1765  gram  Fe  :  then  to  the  same 
food  lor  a  similar  length  of  time  were  added  0.441  grain  Fe  (as  sulphate),  making  in  all 
0.636  gram  Fe,  and  of  this  0.6084  gram  were  recovered  in  the  excreta.6  This  experiment 
proves  only  that  such  absorption  as  may  take  place  is  pretty  nearly  balanced  by  the  excre- 
tion.     Alter  eating  hi 1   the  feces  are  found  to  contain  much  hiematin.  and  it  has  been 

thought  that  iron  could  not  be  absorbed  in  that  way.  hut  Abderhalden8  has  recently  shown 
that  there  can  he  a  small  amount  of  iron  absorption  after  feeding  either  haemoglobin  or 
h;ematin.  Bunge  ha-  sought  for  one  of  the  antecedents  of  haemoglobin  in  egg-yolk, 
and  ha>  described  it  as  an  iron-containing  nucleo-albumin,  which  he  names  haematogen. 
That  and  similar  aucleo-albumins  existing  in  plants  he  conceives  to  he  the  source  of 
absorbable  iron,  while  inorganic  salts  of  iron  aid  only  indirectly  by  forming  iron 
sulphide,  thus  preventing  the  same  formation  from  organic  iron  (see  above).  Small 
amounts  of  absorbable  iron  are  found  in  all  the  ordinary  cereal  foods.7      .Marion"  has 

'  Macallum  :  Journal  of  Physiology,  1894.  vol.  1.5,  p.  268. 

2  Forster:  Zetochrifl  fur  Bioloijie,  1873,  Bd.  9,  S.  297.  3  Lor.  cit. 

1  This  figure  is  probably  too  high,  but  the  principle  itself  is  fundamental.  See  Voit, 
Hermann*  Handbook,  1881,  vi.  1,  S.  385. 

5  Hamburger:  Zeitschrifl  fur  physiologische  Chemie,  1878,  Bd.  2,  S.  191. 

f'  Zeitschrifl  fur  Biohgie,  1900,  Bd.  39,  S.  487. 

7  Bunge:  Zeitschrifl j'iir  ph>i.<ioo>t/i.<rhc  <%-mi,\  ls;)s,  p„j.  25,  S.  36. 

h  Archivfiir  exper.  Pathologic  und  Pharmakologie,  1891,  Bd.  29,  S.  212. 


THE   CHEMISTRY  OE   THE  ANIMAL   BODY.  529 

prepared  a  substance  from  proteid  and  iron  salts,  called  ferratin,  which  contains  4  to  8 
per  cent,  of  iron ;  it  is  a  compound  unaffected  by  gastric  juice  or  by  boiling ;  it  is  solu- 
ble in  the  alkaline  intestine,  where  it  is  but  slowly  affected  by  alkaline  sulphide.  Now 
this  same  ferratin  is  found  in  the  body  itself,  especially  in  the  liver,1  although  not  the  only 
iron-containing  substance  of  the  liver.2  If  ferratin  be  fed,  the  quantity  of  it  increases  in 
the  liver.  If  a  dog  be  fed  on  milk,  which  is  always  poor  in  iron,  and  he  be  bled  from 
time  to  time,  the  ferratin  disappears  from  the  liver,  being  used  for  the  formation  of  new 
red  blood-corpuscles.3  Such  a  liver  does  not  change  color  when  placed  in  dilute  ammo- 
nium sulphide,  while  one  containing  ferratin  or  other  iron  compounds  gradually  turns  black 
from  iron  sulphide.  If  milk  containing  ferratin  be  fed,  the  ferratin  may  be  deposited  in 
the  liver  for  the  use  of  the  blood.  As  it  is  not  decomposed  by  boiling,  ferratin  is  found  in 
the  usual  cooked  meat.  Concerning  the  influence  of  inorganic  salts,  Selimiedeberg  agrees 
with  Bunge  that  the  formation  of  iron  sulphide  protects  the  ferratin  from  attack. 

The  insolubility  of  iron  salts  in  alkaline  solutions  has  raised  the  question  of  their 
absorption  by  the  blood.  If  inorganic  iron  salts  be  injected  into  a  vein,  the  iron  reappears 
chiefly  in  the  intestines,  with  only  3  to  4  per  cent,  in  the  urine  (Jakobj):  in  too  great 
quantities  they  have  powerful  toxic  properties.  Gottlieb4  administered  0.1  gram  of  iron 
as  sodium  iron  tartrate  subcutaneously  to  a  dog  during  a  period  of  nine  days ;  twenty-eight 
days  after  the  first  injection  0.0969  gram  Fe  had  been  removed  in  the  excreta  over  and 
above  the  normal  excretion  calculated  for  the  same  time.  It  was  shown  that  this  iron  was 
especially  stored  in  the  liver.  It  may  be  argued  that  such  iron,  being  foreign  to  the  organ- 
ism, was  deposited  in  the  liver  and  gradually  excreted  as  other  heavy  metals,  mercury, 
copper,  lead,  would  be.  Kunkel5  fed  mice  and  to  the  food  of  half  their  number  added  a 
solution  of  oxychloride  of  iron  (FeCl3,4Fe(OH)3,  liquor  ferri  oxychlorati) :  in  the  livers  of 
those  fed  with  iron,  iron  was  present  to  a  greater  extent  than  in  the  others ;  but  here, 
again,  the  surplus  can  be  attributed  to  the  sulphide-forming  protective  power  of  the  added 
salts,  which  Kunkel  admits,  though  maintaining  the  contrary  ground.  The  proof  of  the 
absorption  of  inorganic  salts  emanates  from  Macallum,6who  showed,  after  feeding  chloride, 
phosphate,  and  sulphate  to  guinea-pigs,  that  the  epithelial  cells  and  the  subepithelial 
leucocytes  of  the  intestines  gave  a  strong  microchemical  reaction  for  iron  with  ammonium 
sulphide.  With  small  doses  this  was  observed  only  near  the  pylorus,  for  iron  is  soon  pre- 
cipitated by  the  alkali  of  the  intestines,  but  where  the  iron  salt  was  in  sufficient  quantity 
to  neutralize  the  intestinal  alkali  it  coidd  be  absorbed  the  whole  length  of  the  small  intes- 
tine. Whether  inorganic  iron  unites  with  proteid  before  absorption  or  not  is  unknown. 
According  to  Swirski,  the  absorbed  iron  compounds  pass  into  the  lymph  or  into  the  blood 
of  the  portal  vein.  In  the  latter  they  are  taken  up  by  the  leucocytes  (phagocytes)  and 
carried  to  the  liver.  Fasting  guinea-pigs  which  have  been  prevented  by  muzzling  from 
eating  their  feces  and  thus  deprived  of  even  a  small  quantity  of  iron,  are  more  susceptible 
to  disease  than  the  same  unmuzzled  annuals.  The  iron-containing  phagocytes  are  believed 
to  destroy  bacterial  poisons. 

Regarding  the  transformation  of  iron  compounds  after  absorption  into  haemoglobin, 
little  is  known  except  that  the  necessary  synthesis  takes  place  in  tin'  spleen,  in  the  bone- 
marrow,  and  probably  in  the  liver.  On  the  destruction  of  red  blood-corpuscles,  proteid 
bodies  holding  iron  in  combination  are  deposited  in  the  cells  of  the  liver,  spleen,  bone- 
marrow,  and  kidney,7  this  being  noticeable  in  pernicious  anaemia.     On  the  production  of 

1  Marfori,  he.  cit,  and  Selimiedeberg,  Archiv  fiir  exper.  Pathologie  mid  Pharmakohgie,  1894, 
Bd.  33,  S.  101. 

'  Vav  :  Zeitschrift  fur  physiologisehe  Chemie,  1895,  Bd.  20,  S.  398. 

3  Schmiedeberg,  Op.  cit.,  S.  110. 

*  Zeitschrift  fiir  physiologische  Chemie,  1891,  Bd.  15,  S.  371. 

5  Pjliiger's  Archiv,  1891,  Bd.  50,  S.  11. 

6  Swirski:  Ibid.,  1899,  Bd.  74,  S.  4G6 ;   Journal  of  Physiology,  1894,  vol.  16,  p.  268. 
1  Schurig;  Archiv  fur  exper.  Pathologic  nml  Pharmabtlmjir,  lS'.ts,  p,J.  41,  s.  29. 

Vol.  l.—U 


530 


AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 


icterus  with  arseniuretted  hydrogen,  similar  iron  compounds  are  noted  in  the  liver,  being 
cleavage  products  of  haemoglobin  in  its  transformation  to  biliary  coloring  matter.  The 
amount  of  iron  normally  excreted  from  the  body  is  far  less  than  the  corresponding  biliary 
coloring  matter  (see  Haemochromogen),  showing  that  the  rest  of*  the  iron  is  retained  for 
further  use  in  constructing  new  haemoglobin.  After  extirpation  of  the  spleen  the  amount 
of  coloring  matter  in  the  bile  may  decrease  more  than  one-half,  indicating  that  biliary 
coloring  matter  is  normally  formed  in  the  spleen  through  the  destruction  of  haemoglobin, 
and  is  carried  by  the  portal  vein  to  the  liver.1 

Iron  is  excreted  as  phosphate  in  the  gastric  juice,  in  bile  (in  considerable  quantity),  and, 
according  to  MacaUum,"  in  the  intestinal  juice.  In  the  urine  it  is  present  as  an  unknown 
organic  compound. 

A  newborn  child  or  animal  lias,  proportionately  to  its  weight,  far  more  iron  than  at  any 
other  time  of  its  life.  This  iron  is  lost  only  very  slowly,  hence  the  very  small  quantity  of 
iron  in  the  milk  answers  all  necessities.  The  other  salts  of  the  milk  are  in  the  same  pro- 
portion to  one  another  as  are  the  salts  in  the  newborn  animal. 

Tables  representing  generally  accepted  analyses  of  the  mineral  constituents  of  the  more 
important  fluids  and  cells  of  the  body  are  subjoined.  Only  very  pronounced  differences 
are  to  be  taken  into  consideration  in  drawing  conclusions,  for  analyses  of  animals  of  dif- 
ferent species,  or  of  the  same  species,  or  even  of  the  same  animal  at  different  times,  show 
wide  variations.     The  tables  represent  parts  in  1000  of  fresh  substance : 


K0SO4. 

KC1. 

NaCl. 

NajC03. 

CaC03. 

Ca3P04. 

MgC03. 

Mg3(P04)a. 

FeP04. 

Salivas  (dog)   .   .   .   .      0.209 
Pancreas  *  (dog)    .  .      ... 
Gastric  juice6  (dog).      .  .   . 
Fresh  bile6  (dog)  .   .  i    0.022 

0.940 

0.93 

1.125 

1.546 

2.53 

2.507 

o.ias 

0.940 

3.30(Na2O) 

0.056 

0.150 

0.624(CaOa) 
0.030 

0.113 
0.07 
1.729 
0.039 

O.Ol(MgO) 
0.007(MgO) 

0.01 

0.226 

.... 

0.082 
0.021 

II. 


Blood-serum7  (dog)    .   . 

I'.l 1-corpuscles*  (pig) 

Blood-serum 8  (pig)    •  • 

Muscle ,J  i<>.\  1     

Milkio(cow) 


K20. 

Na20. 

CaO. 

MgO. 

Fe2Os, 

CI. 

0.202 

4.341 

0.176 

0.041 

0.01 

3.961 

5.543 

0 

0 

0.158 

1.504 

0.  "7:: 

4.272 

0.136 

o.(i:;s 

3.611 

1  6   1 

0.770 

0.086 

11,112 

0.057 

0.672 

1.07 

1.05 

1.51 

0.20 

0.003 

1.86 

P206. 


0.489 
2.067 
0.188 
4.644 
1.60 


1  Pugliese:  Archiv  fur  Phydologie,  1899,  S.  80.  2  Op.  cit.,  p.  278. 

:t  Ilerter:  Hoppe-Sevler's  Physiologische  Chemie,  S.  192. 

4  Kroger :  Quoted  by  Halliburton,  Chemistry,  Physiological  and  Pathological,  p.  656. 

5  Bidder  and  Schmidt:  Quoted  by  Halliburton,  Op.  cit.,  p.  638. 
'  Boppe-Seyler  :  Physiologische  Chemie,  S.  302. 

7  Bunge :  Bid.,  3d  ed.,  S.  265. 

8  Op.  rit.,  S.  222.      For  other  similar  blood  analyses,  see  Abderhalden,   Zeitschrift  fur 
physiologische  Chemie,  1898,  Bd.  2-"),  S.  65. 

9  Bunge  :  Ibid.,  1885,  Bd.  9,  S.  60. 

10  Bunge  :  Physiologische  Chemie,  3d  ed.,  S.  100. 


THE   CHEMISTRY   OE   THE  ANIMAL    BODY.  531 

THE  CHEMISTRY  OP  THE  COMPOUNDS  OF  CARBON. 

Derivatives  of  Methane. 

The  complicated  structure  aud  the  great  variety  of  the  compounds  of  car- 
bon are  due  to  the  fact  that  carbon-atoms  have  a  greater  power  for  union 
with  one  another  than  have  the  atoms  of  other  elements. 

Saturated  Hydrocarbons  or  Paraffins  (formula,  C„H2n  +  2 ). — 

Methane,  CH4,  gas.  Pentane,  C5H12,  liquid  at  38°. 

Ethane,  C2H6,     "  Hexane,  C6H14.  "     71°. 

Propane,  C3H8,    "  Heptane,  C7H16,  "     98°. 

Butane,  C4H10,    "  etc. 

These  are  the  constituents  of  petroleum  and  natural  gas,  and  are  formed  by  the  action 
of  low  heat  on  coal  under  pressure  in  the  absence  of  oxygen,  and  are  probably  derived 
from  fossil  animal  fat,  since  it  has  been  shown  that  the  paraffins  may  be  obtained  in  large 
quantity  by  beating  fish  oil  at  a  pressure  of  ten  atmospheres.1  The  paraffins  may  all  be 
formed  synthetically  from  methane  by  the  action  of  sodium  on  halogen  compounds  of  the 
group : 

2CH3I  +  2Na  =  C2H6  +  2NaI. 

C2H5I  +  CH3I  +  2Na  =  C3H8  +  2NaI. 

This  may  be  continued  to  form  a  theoretically  endless  number  of  compounds.  Paraffins  are 
notably  resistant  to  chemical  reagents,  not  being  affected  by  either  concentrated  nitric  or 
sulphuric  acids.  Vaseline  contains  a  mixture  of  paraffins  melting  between  30°  and  40°. 
By  massage  vaseline  may  be  absorbed  by  the  skin,  through  the  epithelial  cells  of  the  seba- 
ceous glands.  In  rabbits  and  dogs,  directly  after  such  treatment,  it  may  be  detected  de- 
posited especially  in  muscle,  but  it  is  for  the  greater  part  destroyed  in  the  body.2 

Monatomic  Alcohol  Radicals. 

These  are  radicals  which  may  be  considered  as  paraffins  less  one  atom  of  hydrogen,  and 
therefore  having  one  free  bond.  They  form  the  basis  of  homologous  series  of  alcohols 
and  acids. 

Monatomic  Alcohols  (general  formula,  CnH2n  +  jOH). — 

Methyl  alcohol,  CH,OH.  Amyl  alcohol,  C5H„OH. 

Ethyl  alcohol,  C2H501I.  Hexyl  alcohol,  C„H13OH. 

Propyl  alcohol,  CBHTOH.  Heptyl  alcohol,  CTHuOH. 
Butyl  alcohol,  C4H9OH.  etc. 

General  Reactions  for  Primary  Alcohols.— (1)  Alcohols  treated  with  sulphuric  acid 
give  ethers  (see  Ethyl  ether) : 

2CH3OH  +  h2so4  =  ch:;>°  +  H*°  +  H2SOi< 

Methyl  ether. 
(2)  Alcohols  oxidized  give  first  aldehyde  and  then  acid : 
CHsOH  +  0  =  HC  ^g  +  H20. 

Methyl  aldehyde. 

CH20  +  0  =  HC<£JH 

Formic  acid. 

1  Engler:  Berichte  der  deutschen  chemischen  OeseUachaft,  1888,  Bil.  21,  S.  1816. 

1  Soubiranski :  Archivfiir  exper.  Pathologie  und  Pharmakologie,  1893,  Bd,  31,  S.  329. 


532  AN  AMERICAN    TEXT-BOOK   OF   PHYSIOLOGY. 

■    Primary  alcohols  may  be  prepared1  by  reduction  of  the  aldehyde  with  nascent 

hydrogen, 

<H;niO  +  H.2  =  ril  rn  OH 

Ethyl  aldehyde.  Ethyl  alcohol. 

and  similarly  by  reduction  of  the  acid. 

Secondary  Alcohols.  -Prom  propyl  alcohol  upward  there  are  alcohols  isomeric  with  the 
primary  alcohols,  but  in  which  the  grouping  11 — CIIOII — 11  is  characteristic.  These  are 
secondary  alcohols,  and  may  be  produced  by  the  action  of  nascent  hydrogen  on  ketones: 

CHs-CO  (II:!  +  H2  =  CH3-CHOH-('ll 

Acetone.  Isopropyl  alcohol. 

Tertiary  Alcohols. — These  have  the  general  formula  R3^-rOH. 
Monobasic  Acids — The  Fatty  Acids  (formula,  CnH2n02). — 

Formic  acid.  II  COOH.  Capric  acid,  C9H19COOH. 

A.,  tic  acid.  CH3COOH.  Laurie  acid,  CnH23COOH. 

Propionic  acid,  C2H5COOH.  Myristic  acid.  C13H.27COOH. 

Butyric  acid,  C3H7COOH.  Palmitic  acid,  C15H31COOH. 

Valerianic  acid,  C+H9COOH.  Stearic  acid,  C17H33CO( )  1 1 . 

( laproic  acid,  C5H„COOH.  Arachidic  acid,  C19H39COOH. 

(Enanthylic  acid,  C6H18COOH.  Cerotic  acid,  C26H53CO<  )1 1 . 

( !aprylic  acid,  C7H15COOH.  Melissic  acid,  C29H59COOH. 

These  are  organic  compounds  of  acid  reaction  in  which  one  atom  of  hydrogen  is  replace- 
able by  a  metal  or  an  organic  radical.  Combined  with  glycerin  the  higher  members  of  the 
series  (from  (',  up)  form  the  neutral  fats  of  the  organism.  By  distillation  of  a  fatty  acid 
with  alkaline  hydrate,  a  hydrocarbon  is  obtained  containing  one  carbon  atom  less  than 
the  acid  used. 

CH3COONa  +  NaOH  =  CH4  +  Na,C03. 

I'n ixiration. — in)  Through  oxidation  of  alcohols  or  of  aldehydes, 

C,,H5OH  +  02  =  CH3COOH  +  H20. 
(b)  Through  the  action  of  carbon  dioxide  on  the  sodium  compound  of  alcohol  radicals, 
CH3Na  +  C02  =  CH3COONa. 

Compounds  op  Methyl. 

Methane,  or  Marsh-gas,  CH4. — This  gas  is  produced  by  intestinal  putre- 
faction, and  is  the  only  hydrocarbon  found  in  the  body.  It  is  formed  iu  largest 
quantities  from  the  fermentation  of  cellulose,  which  takes  place,  according  to 

Hoppe-Seyler,  thus  : 

C6H10O5  +  H20  =  C6H1206. 

C6Hl206  =  3CH4  +  3C02. 

Tappeiner2  finds  that  less  ('1I4  than  C02  is  produced  in  cellulose  fermenta- 
tion in  the  intestine,  and  that  the  lower  fatty  acids  (acetic  to  valerianic)  are 
also  formed.  This  putrefaction  is  especially  great  in  the  caecum  of  herbivora. 
Methane  is  also  a  product  of  putrefaction  of  proteid  (but  not  of  casein,  since 
it  is  not  present  when  milk  is  fed).     Through  the  put  refaction  of  cholin,  a 

1  Again  attention  is  calleil  to  the  fact  that  the  list  of  these  reactions  is  in  no  wise  complete, 
but  only  intended  to  be  suggestive  of  what  .should  he  mastered  from  a  text-book  on  general 
chemistry. 

5  Zeiischrijl  fur  Biologic,  1884,  Bd.  20,  S.  84. 


THE   CHEMISTRY   OF  THE  ANIMAL   BODY.  533 

decomposition  product  of  lecithin,  methane  is  likewise  evolved  in  small 
quantity.1  Further,  methane  may  be  produced  from  the  putrefaction  of  metal- 
lic acetates : 

CaC4H604  +  2H20  =  CaC03  +  C02  +  H20  +  2CH4. 
Properties. — A  colorless,  odorless  gas  which  hums  with  a  dull  flame.  It  is 
absorbed  by  the  blood,  and  in  the  herbivora  is  given  off  by  the  lungs  often  in 
larger  quantity  than  from  the  rectum.2  In  man  only  little  is  produced.  Methane 
is  not  oxidized  in  the  body,  and  is  harmless  when  respired,  even  when  10  or  20 
per  cent,  in  volume  is  present.3 

Trichlormethane,  or  Chloroform,  CHC13. — This  temporarily  paralyzes  nerves  and 
nerve  centres.  It  is  principally  removed  as  vapor  through  the  lungs,  but  is  partially 
burned,  thereby  increasing  the  inorganic  chlorides  in  the  urine.4  After  giving  chloroform 
it  may  itself  occur  in  the  urine,  and  likewise  a  substance  which  reduces  Fehling's  solu- 
tion, glycuronic  acid  (which  see). 

Methyl  Aldehyde,  or  Formic  Aldehyde,  H.CHO. — This  may  be  pro- 
duced synthetically  by  passing  vapor  of  methyl  alcohol  mixed  with  air  over 
an  ignited  platinum  spiral, 

CH3OH  +  O  =  H.CHO  +  H20. 

On  cooling  the  vapor,  the  aldehyde  is  found  dissolved  in  the  alcohol.  On 
evaporation  of  the  alcohol,  the  aldehyde,  through  condensation  of  three  of 
its  molecules,  forms  a  crystalline  body  having  the  composition  (HCHO)3  and 
called  paraformic  aldehyde.  This  latter  treated  with  calcium  or  magnesium 
hydrate  again  suffers  condensation  with  the  production  of  formose,  C6H1206,  a 
sweet-tasting  sugar  (Butlerow,  Loew)  identical  with  ^-fructose  (Fischer). 
Baeyer5  first  suggested  that  the  sugar  synthesis  in  the  plant  was  analogous 
to  the  above  process.  He  conceived  the  reduction  of  carbon  dioxide  to 
carbon  monoxide,  which  united  with  chlorophyll,  and  afterward  through 
hydrogen  addition  became  formic  aldehyde ;  then  in  upward  stages  became 
metaformic  aldehyde,  sugar,  starch,  and  cellulose.  Reinke6  has  shown  the 
presence  of  formic  aldehyde  in  chlorophyll  leaves,  and  believes  its  produc- 
tion due  to  the  reduction  of  carbonic  acid  through  the  power  of  the  sun 
on  the  leaf,  thus : 

H2C03  =  HCHO  +  02. 

Bach 7  states  that  carbonic  acid  and  water  in  the  presence  of  uranium  acetate 
yield  formic  aldehyde  and  nascent  oxygen  when  placed  in  the  sun.  According 
to  Stocklasa,8  400  grams  of  fresh  leaves  (128  grams  dry)  of  the  sugar  beet 

1  Hasebroek:  Zeitschrift  fitr  physiologische  Chemie,  1888,  Bd.  12,  S.  148. 

2  B.  Tacke :  Quoted  by  Bunge,  Physiologisehe  Chemie,  3d  ed.,  1894,  S.  -JS  1. 

8 Paul  Bert:  Complex  rendus  de  la  Societe  de  Biologic,  188*>,  p.  ,VJ3.  Abstract  in  Malay's 
Jahresbericht  iiber  Thierchemie,  1886,  Bd.  16,  8.  364. 

4  A.  Zeller:  Zeitschrift  fur  physiologische  Chemie,  1883,  Bd.  8,  S.  74. 

5  Beriehte  der  dcutschen  chemischen  Gesellschaft,  1870,  Bd.  3,  S.  67. 

6  Ibid.,  1881,  Bd.  14,  S.  2144. 

7  Ibid,,  1894,  Bd.  26,  S.  502  and  689. 

8 Stocklasa:  Zeitschrift  fiir  physiologische  Chemie,  1896,  Bd.  21,  S.  83. 


534  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

form  synthetically  and  send  to  the  beet  root  31  grams  of  cane-sugar  in 
thirty  days. 

General  Behavior  of  Aldehydes. — They  act  as  reducing  agents,  being  readily  oxidized 
to  the  corresponding  acid.  With  nascent  hydrogen  they  are  reduced  to  alcohols.  A  dis- 
tinctive reaction  of  aldehydes  and  ketones  is  their  union  with  phenyl  hydrazin,  C6II5 — 
NH — NIL.  giving  hydraxones : 

CH3CHO  +  CSH5XI1XII2  =  CH3.CH:N.NH.C«HS  +  H20. 

Preparation. — By  distillation  of  the  salt  of  an  acid  with  a  salt  of  formic  acid : 
CH3COONa  +  HCOONa  =  Na2C03  +  CH3CHO. 

Aceto-aldehyde. 

Methyl  Mercaptan,  CH3SH. — This  is  a  product  of  bacterial  action  on 
proteid,1  and  is  found  with  H2S  in  the  intestine.  It  is,  furthermore, 
given  off  on  fusing  proteid  with  potash.2  Methyl  mercaptan  boils  at  5°, 
and  has  a  strong  odor.  It  is  found  in  the  urine,  especially  after  eating 
asparagus,  giving  to  it  a  peculiar  smell.3  According  to  Rubner i  the  smell  of 
cooked  cabbage,  cauliflower,  and  the  like,  is  due  to  methyl  mercaptan. 

Methyl  Telluride,  (CH8)2Te. — A  gas  of  penetrating  odor  found  in  all  excreta  of  an 
animal  after  feeding  salts  of  telluric,  H,Te04.  or  tellurious,  H2Te03,  acid.  The  salt  is  re- 
uuced  to  metallic  tellurium  in  the  body,  which  unites  with  a  methyl  group  in  some  way 
liberated  in  the  cells.5  Metallic  tellurium  may  be  microscopically  seen  deposited  in  various 
cells,  and  the  odor  of  (CH3)2Te  may  be  detected  for  months  after  the  last  dose  has  been 
given  to  a  dog.8 

Methyl  Selenide,  (CH3)2Se. — This  is  very  similar  to  the  last-named  substance,  but 
more  poisonous. 

Formic  Acid,  HCOOH. — Found  in  ants,  and  obtained  by  distilling  them 
with  water.  Present  likewise  in  stinging-nettles  and  in  the  sting  of  honey- 
bees, wasps,  and  hornets,  although  not  the  essential  poison.7  Its  salts  are 
found  in  minute  quantities  in  normal  urine,  and  are  present  especially  in  both 
blood  and  urine  in  such  diseases  as  leucocythsemia,  fever,  diabetes.8  Formic 
acid  may  be  obtained  from  the  oxidation  of  methyl  alcohol,  of  sugar,  and  of 
starch,  but  not  from  the  latter  two  in  the  body.  Likewise  by  heating  oxalic 
acid, 

COOH 

cooii  =  HCOOH  +  co" 

It  is  found  in  the  urine  after  feeding  methyl  alcohol  and  other  methyl  deriv- 
atives,  such  as  oxymethyl-sulfonic  acid,  or  formic;  aldehyde.  Ethyl  alcohol,  on 
the  contrary,  does  not  yield  it.9  It  is  the  lowest  member  of  the  fatty-acid  series, 
the  most  volatile,  and  the  least  readily  oxidized  in  the  body.    If  formates  be 

1  M.  Nencki  :  Archiv  fur  exper.  Pathologic  und  Pharmakologie,  1891,  Bd.  28,  S.  206. 

2  M.  Rubner  :  Archiv  fiir  Hygiene,  1S93.  :t  Nencki,  loe.  eit  *  Loc  cit. 
Bofmeister:  Archiv  fiir  exper.  Pathologic  wad  Pharmakologie,  ]s94,  Bd.  33,  S.  198. 

8  Beyer:   Archiv  fur  Physiologic,  Jahrgang  L895,  S.  225. 

7  Langer :  Archiv  fur  exper.  Pathologic  und  Pharmakologie,  1897,  Bd.  38,  S.  381. 

8  See  R.  Jaksch :  Zeitechrift  fiir  ph^ulnji^lt,  ('/„  ,,,;,-,  ism;,  r,d.  10,  S.  537. 

9  Pohl:  Archiv  fur  exper.  Pathologic  und  Pharmakologie,  1893,  Bd.  31,  S.  298. 


THE   CHEMISTRY  OE   THE    ANIMAL   BODY.  535 

fed  they  appear  readily  in  the  urine.  It  has  a  penetrating  odor,  acts  as  a 
reducing  agent  (HCOOH  -f-  O  =  COa  +  H20),  and  therefore  precipitates 
Fehling's  solution.  Outside  of  the  body  it  readily  undergoes  oxidation  to 
water  and  carbonic  acid.  It  produces  inflammation  of  the  skin.  A  7  per 
cent,  solution  given  to  a  rabbit  per  os  has  a  most  powerful  corrosive  action  and 
results  fatally,  formic  acid  being  found  in  the  urine. 

Ethyl  Compounds. 

Ethyl  Hydroxide,  or  Ethyl  Alcohol,  C2H5OH. — This  has  been  detected 
in  minute  quantity  in  the  normal  muscle  of  rabbits,  horses,  and  cattle.1 
Yeast-cells  produce  a  ferment,  zymase,  which  acts  to  split  dextrose  into  alcohol 
and  carbonic  acid,  producing  likewise,  to  a  very  small  extent,  the  higher 
alcohols,  propyl,  isobutyl,  amyl,  the  esters  of  the  fatty  acids  (fusel  oil), 
glycerin,  and  succinic  acid.  Such  fermentation  may  to  a  small  extent  take 
place  in  the  intestine,2  and  likewise  in  the  bladder  (occurrence  in  diabetic- 
urine).  Pure  alcohol  is  a  colorless,  almost  odorless  liquid,  having  a  burning 
taste.  It  is  a  valuable  solvent  of  resins,  fats,  volatile  oils,  bromine,  iodine, 
and  many  medicaments. 

Tinctures  are  alcoholic  solutions  of  various  drugs  and  salts. 

Liqueurs  are  manufactured  from  alcohol  properly  diluted,  and  treated  with  sugar  and 
characteristic  ethereal  oils  and  aromatics. 

Distilled  liquors  are  obtained  by  the  distillation  of  the  fermentative  products  of  various 
substances,  whiskey  from  corn  and  rye,  rum  from  molasses,  brandy  from  wine.  The  cha- 
racterizing taste  depends  on  the  different  ethereal  and  fusel  oils. 

Wines  are  produced  from  the  natural  fermentation  of  grape-juice.  Sherry,  madeira, 
and  port  are  fortified  by  the  further  addition  of  alcohol  and  sugar. 

Beer  is  made  by  converting  the  starch  of  barley  into  maltose  and  dextrin  through 
diastase.  To  an  aqueous  solution  of  the  above  hops  are  added,  and  the  whole  is  boiled. 
After  the  settling  of  precipitated  proteid,  etc.,  the  clear  supernatant  fluid  is  drawn  oflf  and 
treated  with  yeast,  with  ultimate  conversion  into  beer.    The  taste  is  furnished  by  the  hops. 

Alcohol  in  the  Body. — Alcohol  in  the  stomach  at  first  prevents  the 
gelatinization  necessary  in  proteid  for  peptic  digestion,  but  this  difficulty  is  of 
no  great  moment  because  the  absorption  of  alcohol  is  rapid  and  complete. 
It  makes  the  mucous  membrane  hyperaemic,  promotes  the  absorption  of 
accompanying  substances  (sugar,  peptone,  potassium  iodide),  and  stimulates 
the  flow  of  the  gastric  juice.3  In  this  matter  it  acts  as  do  other  condiments 
(salt,  pepper,  mustard,  peppermint),4  but  if  there  be  too  great  an  irritation 
on  the  mucous  membrane  there  is  less  activity  (dyspepsia).  The  rapid 
absorption  gives  to  alcohol  its  quick  recuperative  effect  alter  collapse,  and 
it-  value  in  administering  drugs,  especially  antidotes.  Alcoholic  beverages 
combining  alcohol  and  flavor  promote  gastric  digestion  and  absorption,  but 
often  stimulate  the  appetite   in  excess  of  normal   requirement      Alcohol   is 

^ajewski:    Pfliiger's  Archiv,  1875,  Bd    II.   S.  122 

-  Macfadyen,  Nencki,  and  Sieber :  Archiv  fiir  exper.  Pathologic  wnd  Pharmakologie,  1891,  Bd. 
28,  S.  347. 

3  Brandl:  Zeitsehrifl  fur  Biologie,  L892,  Bd.  29,  S.  277.  Chittenden,  Mendel,  and  Jackson: 
American  Journal  of  Physiology,  1808,  vol.  i.  p.  164.  4  Brandl,  Op.  cit.,  8.  292. 


536  AN   AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

burned  in  the  body,  but  may  also  be  found  in  the  breath,  perspiration,  urine, 
and  milk.  Alcohol  has  no  effect  on  proteid  decomposition,  but  acts  to  spare 
tat  from  combustion.1  The  addition  of  50  to  80  grams  of  alcohol  to  the 
food  has  no  apparent  effect  on  the  nitrogenous  equilibrium.2  Alcohol  in  the 
body  acts  as  a  paralyzant  on  certain  portions  of  the  brain,  destroying  the  more 
delicate  degrees  of  attention,  judgment,  and  reflective  thought,  diminishing  the 
sense  of  weariness  (use  after  great  exertion — furnished  to  armies  in  the  last 
hours  of  battle)  and  raising  the  self-esteem  ;  it  paralyzes  the  vaso-constrictor 
nerves,  producing  turgescence  of  the  skin  with  accompanying  feeling  of  warmth 
and  therein'  indirectly  aiding  the  heart.'5  Alcohol  acts  to  stimulate  the  res- 
piration especially  in  the  tired  and  weak,  wine  with  a  rich  bouquet  like  sherry 
being  more  effective  than  plain  alcohol.'  The  higher  alcohols,  propyl,  butyl, 
amyl  (sec  p.  539),  are  more  poisonous  as  the  series  ascends,0  and  are  less  vol- 
atile, less  easily  burned,  and  therefore  more  tenaciously  retained  by  the  body, 
with   more  pernicious  result-. 

Ethyl  Ether,  C2H5.O.C2H5. — This  is  formed  by  the  action  of  sulphuric  acid  on 
alcohol,  thus  : 

C2H5OH  -  H2S04  =  C2H5HS04  +  H20. 

C2H5HS04  +  C2H5OH  =(C2H5)20  +  H2S04. 

Ether  is  a  solvent  for  fats,  resins,  and  ethereal  oils.  Respired  with  air  its  action  is  like  that 
of  chloroform,  producing  temporary  paralysis  of  the  nerves  and  nervous  centres.  Since  it 
boils  at  35.5°  its  tension  in  the  blood  is  always  high,  and  it  is  probably  not  burned  in  the 
body  to  any  great  extent,  but  when  present  is  eliminated  through  the  breath. 

Ethers  in  general  are  neutral  and  very  stable  bodies,  and  may  be  considered  oxides  of 
organic  radicles.  They  may  all  be  prepared  by  boiling  the  corresponding  alcohol  with  sul- 
phuric acid.  Mixed  ethers,  in  which  the  radicles  are  different,  are  prepared  by  boiling  two 
different  alcohols  with  sulphuric  acid  : 

CH8HSO,  +  C2H5OH  =  CH3OC2H5  +  H2S04. 

Methyl-ethy]  ether. 

Chloral  Hydrate,  CCl,CHO  +  H,0  or  CClsCH(OH)2.— This  is  thehydrated  form  of 
trichlor-ethyl  aldehyde,  CCl3CHO,  and  is  used  as  an  anaesthetic.  It  is  an  interesting  fact 
that  when  fed  it  partially  reappears  in  the  urine  as  urochloralic  acid,  which  consists  of 
trichlor-ethyl  alcohol,  (T13CH,0II,  combined  with  glycuronic  acid  (which  see).  This  is  a 
notable  illustration  of  reduction  in  the  body,  the  change  from  an  aldehyde  to  an  alcohol. 

Acetic  Acid,  CH3COOH. — Acetic  acid,  the  second  of  the  fatty-acid  series, 
is  found  in  the  intestinal  tract  and  in  the  feces,  being  a  product  of  putrefaction 
(see  p.  545).  It  is  more  easily  burned  than  formic  acid,  and  when  absorbed  is 
resolved  into  C02  and  water.  It  is  found  in  traces  in  the  urine,  the  total 
amount  of  fatty  acids  normally  present  being  0.008  gram  per  day.6  Like 
formic  acid,  and  accompanied  further  by  the  higher  acids  of  the  series,  it  is 
present  in  the  blood,  sweat,  and  urine  in  leucocythaemia  and  diabetes.     The 

1  See  Rosemann  :  Pfluger'a  Arehiv,  1899,  Bd.  77,  S.  405. 

2  Strdm:  Abstract  in  Centralblalt fur  Physiologic,  1894,  Bd.  8,  S.  582. 

3  Schmiedeberg :   Grundriss  der  Arzneimittellehre,  2d  ed.,  1888. 
*  Wendelstadt  :    Pfluger'a  Arehiv,  1-99,  Bd.  76,  S.  226. 

&  Gibbs  and  Reichert:  Arehiv  fur  Physiologic,  1893,  Suppl.  Bd.  S.  201. 
«  V.  Jaksch  :  Z(  itschrift  fur  physiologische  Chemie,  1880,  Bd.  10,  S.  536. 


THE   CHEMISTRY   OF  THE  ANIMAL   BODY.  537 

probability  that  acetone  is  derived  from  fat  renders  it  possible  that  these  aeids 
may  also  be  derived  from  fat,  and  not  from  abnormal  proteid  decomposition, 
as  was  formerly  supposed. 

Acetic  acid  is  the  product  of  the  oxidation  of  alcohol.  This  may  be 
brought  about  through  the  presence  of  spongy  platinum,  or  through  the  action 
of  bacteria  (Mycoderma  aceti)  on  dilute  alcohol  (preparation  of  vinegar,  sour- 
ing of  wine :  for  reaction  see  p.  532).  Acetic  acid,  as  well  as  other  higher  fatty 
acids,  is  one  of  the  products  derived  from  proteid  through  its  putrefaction,  its  dry 
distillation,  its  fusion  with  potash,  and  its  digestion  with  baryta  water  in  sealed 
tubes.  Formic,  acetic,  and  propionic  acids  are  products  of  dry  distillation  of 
sugar  (formation  of  caramel).  These  facts  are  of  importance  in  their  rela- 
tion to  the  question  of  the  production  of  fat  in  the  body.  Acetic  and  the 
higher  fatty  acids  are,  further,  products  of  the  dry  distillation  of  wood  and 
of  the  fermentation  of  cellulose  (see  p.  532).  Putrefaction  of  acetates  may 
take  place  in  the  intestines,  the  reaction  being  as  follows : 

2CH3COONa  +  2H20  =  Na2C03  +  2CH4  +  H20  +  C02. 

These  products  are  similar  to  those  in  the  marsh-gas  fermentation  of  cellulose. 
Vinegar,  whose  acidity  is  due  to  acetic  acid,  is  used  as  a  condiment. 

Acetyl-acetic  Acid,  or  Aceto-acetic  Acid,  CH3.CO.CH2.COOH. — This 
may  be  considered  as  acetic  acid  in  which  one  H  atom  is  replaced  by  acetyl, 
CH3CO — ;  or  as  /9-keto-butyric  acid.  Treated  with  hydrogen  it  is  reduced 
to  /2-oxybutyric  acid  (CH3.CHOH.CH2.COOH),  which  in  turn  may  be  oxi- 
dized to  the  original  substance.  Aceto-acetic  acid  readily  breaks  up  into  acetone 
and  carbonic  acid : 

CH3COCH2COOH  =  CH3COCH3  +  C02. 

Aceto-acetic  acid,  acetone,  and  /3-oxybutyric  acid  are  found  in  the  urine  sometimes  singly, 
sometimes  together,  and  probably  as  the  result  of  a  metabolism  of  fat.  In  starvation  and 
in  diabetes  there  is  an  increased  excretion  of  these  bodies,  for  there  is  an  Increased  metabo- 
lism of  fat.  Feeding  fat  increases  the  acetonuria,  whereas  feeding  sugar,  which  protects 
the  fat  from  destruction,  decreases  it.1  From  their  chemical  relations  already  mentioned 
these  substances  may  be  regarded  as  of  common  origin,  and  in  confirmation  of  this 
Araki2  has  shown  that  on  feeding  /3-oxybutyric  acid  it  is  oxidized  and  aceto-acetic  acid 
and  acetone  may  be  detected  in  the  urine.  The  production  of  the  two  aeids  seems  to 
further  a  gradual  neutralization  of  the  blood,  ultimately  causing  coma.3  In  the  presence 
of  these  substances  ammonia  runs  high  in  the  urine,  and  in  amounts  proportional  to  their 
excretion  *  (compare  p.  550). 

Aceto-acetic  acid  gives  to  urine  in  the  absence  of  phosphates  a  red  coloration 
with  ferric  chloride  (principle  of  the  reaction  of  Gerhardt). 

Amido-acetic  Acid,  or  Glycocoll,  CH2.NH2.COOH, — This  is  a  substance 
obtained  by  boiling  gelatin  with  acids  or  alkalies.  It  is  found  in  human  bile 
and  in  that  of  other  animals  combined  with  cholic  acid  and  called  glycoeholie 
acid.  Chittenden''  has  found  glycocoll  in  the  muscles  of  Peeten  irradiam. 
It  is  found  in  the  urine  combined  with   benzoic  acid  as  hippuric  acid  after 

'Literature  by  Waldvogel  :  Zeitsehrift  fur  klinische  Mediein,  1899,  Bd.  38,  S.  r>06. 

2  Zeilschrift  fiir  physiologmhe  Chemie,  1893,  Bd.  18,  S.  6. 

3  Miinzer  and  Strasser:  Archiv  fur  exper,  Pathologie  und  Pharmakologie,  1893,  Bd.  32,  S.  372. 
*  Loc.  n't.  5  An»ii/rii  der  Chemie  und  Pharmakologie,  1875,  Bd.  178,  S.  266. 


538  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

feeding  benzoic  acid  or  compounds  which  the  body  converts  into  benzoic  acid. 
In  a  similar  manner  phenaceturic  acid  is  found  in  the  urine  from  the  grouping 
together  of  glycocoll  and  phenyl  aeetic  acid.  Glycocoll  and  urea  are  to  be 
obtained  by  the  decomposition  of  uric  acid  through  hydriodic  acid.  Glycocoll 
form.-  colorless  crystals,  soluble  in  water  and  having  a  sweet  taste. 

Glycocoll  in  th<  Body. — If  glycocoll  be  fed  it  is  absorbed,  burned,  and 
appears  as  urea  in  the  urine.  The  fact  that  dogs,  whose  bile  never  contains 
glycocholic  acid,  nevertheless  excrete  hippuric  acid  after  being  fed  with  ben- 
zoic acid,  indicates  that,  glycocoll  may  be  considered  a  normal  nitrogenous 
decomposition-product  of  proteid.  Its  easy  cleavage  from  gelatin,  a  product 
manufactured  from  proteid  in  the  body,  confirms  this.  Heteroalbumose  pre- 
pared from  fibrin  likewise  yields  glycocoll  on  decomposition.1  Continual  daily 
feeding  of  sufficient  benzoic  acid  to  fasting  or  casein-fed  rabbits  produces  a  con- 
stant excretion  of  hippuric  acid  in  such  a  proportion  to  total  urinary  nitrogen 
as  to  indicate  that  3  to  4  per  cent,  of  the  proteid  molecule  may  be  split  off 
in  metabolism  as  glycocoll.2  Feeding  gelatin  will  not  increase  the  hippuric 
acid  excretion  as  compared  with  the  total  urinary  nitrogen.  So  glycocoll 
may  be  a  cleavage  product  of  both  gelatin  and  proteid  metabolism. 

Amido-  Adds  in  (inn nil. — These  acids,  such  as  glycocoll.  aspartic  acid,  glutamic  acid, 
leucin,  and  tyrosin  are  found  as  putrefactive  products  of  albumin  and  gelatin.  Tn  these 
acids  the  amido-  group  is  very  stable,  and  cannot  be  removed  by  boiling  with  KOH.  Tliey 
are  all  converted  in  the  body  into  the  amide  of  carbonic  acid  (urea).  Amido-  acids  may  in 
general  be  synthetically  formed  by  heating  mono-halogen  compounds  of  the  fatty  acids  with 
ammonia: 

CH2C1C00H  -f  XH3  =  CH2NH2COOH  +  HC1. 

Methyl  Amido-acetic  Acid,  or  Sarcosin,  CII5.NH.CH2.COOH.— This  is  not  found 
in  the  body,  but  is  derived  from  death),  theobromin,  and  caffein  by  heating  with  barium 
hydroxide. 

Propyl  Compounds. 

Normal  or  Primary  Propyl  Alcohol,  CH3CH2CH2OH. — This  is  one  of 
the  higher  alcohols  formed  in  the  fermentation  of  sugar,  and  on  oxidation 
yields  propyl  aldehyde  and  propionic  acid. 

Propionic  Acid,  CH3<  II.,( '(  >(  )II. — Combined  with  glycerin  this  forms  the 
simplest  fat ;  salts  of  this  acid  feel  fatty  to  the  touch.  Propionic  acid  is  a 
product  of  the  dry  distillation  of  sugar,  of  the  butyric-acid  fermentation  of 
milk-sugar,  and  of  the  put  refaction  of  proteid.  It  is  said  to  be  present  in  the 
sweat,  in  the  bile,  and  sometimes  in  the  contents  of  the  stomach.  Like  others 
of  the  lower  fatty  acids,  it  may  partially  escape  oxidation  and  appear  in  traces  in 
the  urine  (see  p.  536). 

..^-Acetyl  Propionic  Acid,  or  Levulic  Acid,  CH3COCII2CH2COOH.— This  is  the  next 
higher  homologue  to  aceto-acetic  acid.  It  has  been  obtained  only  by  boiling  sugars,  espe- 
cially levulose,  with  acid  and  alkalies,  and  since  Kossel  and  Neumann 3  found  that  it  is 
yielded  by  some  aucleins  tiny  conclude  that  this  indicates  the  presence  of  the  carbo- 
hydrate radical  in  these  aucleins. 

1  Spiro:  Zeitschrift  fiir  physiologisehe  Chemie,  1S99,  Bd.  28,  S.  174. 

2  Parker  ami  Lusk  :   American  Journal  of  Physiology,  1900,  vol.  iii.  p.  472. 

3  Verhandlung  der  Berliner  physiologischen  Gesellscbaft,  Arehivfur  Physiologic,  1894,  S.  536. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  539 

Dimethyl  Ketone,  or  Acetone,  CH3CO(  !H3. — This  is  found  normally  in 
the  blood  and  urine,  and  in  especially  large  quantities  in  patients  suffering 
from  an  abnormally  large  decomposition  of  fat  (see  p.  537).  During  the 
first  day  of  starvation  by  Cetti,  the  starvation  artist,  the  amount  of  acetone 
in  the  urine  rose  to  forty-eight  times  that  of  the  day  previous.1  It  may  like- 
wise appear  in  the  breath,  giving  a  characteristic  odor.  Acetone  is  a  product 
of  the  dry  distillation  of  tartaric  and  citric  acids,  of  wood,  and  of  sugar. 
Oxidized,  acetone  yields  acetic  and  formic  acids,  whereas,  treated  with  hydro- 
gen, it  is  resolved  into  secondary  propyl  alcohol.  When  acetone  is  in  the 
urine  it  is  also  found  in  the  intestinal  canal  and  in  the  feces,  probably  by  pas- 
sage through  the  intestinal  wall. 

Butyl  Compounds. 

Normal  Butyric  Acid,  CH3CH2CH2COOH. — Butyric  acid  was  first  found 
in  butter,  combined  with  glycerin.  When  free  it  gives  the  rancid  odor  to 
butter,  and  likewise  contributes  to  the  odor  of  sweat.  It  has  been  detected  in 
the  spleen,  in  the  blood,  and  in  the  urine,  but  usually  only  in  traces.  As  a  pro- 
duct of  putrefaction  of  proteid,  and  especially  of  carbohydrates,  it  is  found  in 
the  intestines  and  in  the  stomach  when  the  acidity  is  insufficient  to  be  bacteri- 
cidal. It  contributes  to  the  unpleasant  taste  after  indigestion,  through  the 
return  of  a  small  portion  of  the  chyme  to  the  mouth.  In  cheese  it  is  a 
product  of  the  putrefaction  of  casein. 

If  starch,  sugar,  or  dextrin  be  treated  with  water,  calcium  carbonate,  and 
foul  cheese,  the  carbohydrates  are  slowly   converted  into  a  mass  of  calcium 
lactate.     On  further  standing  the  lactic  acid  is  resolved  into  butyric  acid  : 
2CH3CHOHCOOH  =  C3H7COOH  +  4H  +  CO,.* 

Lactic  acid. 

Calcium  salts  are  found  to  putrefy  more  readily  than  others,  and  the  carbon- 
ate is  added  above  to  neutralize  any  acids  formed  in  the  putrefactive  process 
which  might  inhibit  the  action  of  the  spores.  This  same  fermentation  takes 
place  in  the  intestinal  tract. 

Iso-butyl  Alcohol,  (CH3)2:  CH.CH2OH.— This  is  found  in  fusel  oil. 
Iso-butyric  Acid,  (CH3)2:  CH.COOH. — This  is  a  product  of  proteid  putrefaction 
and  is  found  in  the  feces. 

Pentyl  Compounds. 

Iso-pentyl  Alcohol,  or  Amyl  Alcohol,  ((,II,),(1II(,II,(,II,()II.—  This  is  the  principal 
constituent  id'  fusel  oil,  producing  the  after-effects  of  distilled-liquor  intoxication.  The 
poisonous  dose  in  the  dog  per  kilogram  for  the  different  alcohols  has  been  found  n>  lie — for 
ethyl  alcohol  5-6  grams,  for  propyl  alcohol  '■'>  grams,  tor  butyl  alcohol  1. 7  grams,  fur  amyl 
alcohol  L.5  grams1  (see  p.  535). 

Iso-pentoic  or Iso- valerianic  Acid,  (CII3)2CH(  Ih,(  ( )(  HI. — This  is  found 
in  cheese,  in  the  sweat  of  the  foot,  likewise  in  the  urine  in  small-pox,  in  typhus, 
and  in  acute  atrophy  of  the  liver.  It  is  a  product  of  proteid  putrefaction,  and 
has  a  most  unpleasant  odor. 

1  Fr.  Miiller:   Berliner  Minische  Wochemchrif^  1887,  S.  128. 

2  Dujardin-Beaumetz  et  Audig6:   Comptea  rendus,  t.  81,  p.  19. 


540  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

Alcohols  containing  More  than  Five  Carbon  Atoms. 

Of  these,  cetyl  alcohol,  C„dl,,<  )II.  is  found  combined  with  palmitic  acid  in  spermaceti; 
cerotyl  alcohol^  C.,7II  <MI  .  is  found  as  an  ester  in  Chinese  wax;  and  melicyl  alcohol, 
CsqHqOH,  is  combined  with  palmitic  acid  in  beeswax. 

Acids  containing  More  than  Five  Carbon  Atoms. 

Caproic  Acid,  CsHMCOOH. — This  is  formed  from  the  putrefaction  of 
proteidj  being  found  in  cheese  and  in  feces  j  it  may  likewise  be  detected  in  the 
sweat.     United  with  glycerin  it  occurs  in  butter-fat. 

Iso-butyl  Amido-acetic  Acid,  or  Leucin,  (CH3)2 :  CH.CH2.CHNH2. 
COOH. — This  substance  is  a  constant  product  of  proteid  putrefaction,  is  there- 
fore found  in  cheese,  and  may  likewise  be  obtained  by  boiling  proteid  or  gelatin 
with  sulphuric  acid  or  with  alkali.  When  fed  it  is  converted  into  urea.  When 
fed  to  birds  the  tissues  decompose  it  with  elimination  of  ammonia,  which  latter 
may  be  converted  into  uric  acid  by  the  liver.1  It  is  said  to  occur  in  pancreatic 
juice.  According  to  Kiihne  it  is  produced  in  trypsin  proteolysis  to  the  extent 
of  9.1  per  cent,  of  the  proteid  used.  Since  this  weakly  alkaline  medium  in 
pancreatic  digestion  is  especially  favorable  to  bacterial  activity,  Kiihne  added 
antiseptic  salicylate  of  sodium  and  still  found  leucin  (and  tyrosin).  The  same 
results  are  obtained  with  thymol.  It  is  generally  accepted  that  leucin  (and 
tyr<  >sin)  are  normal  products  of  tryptic  digestion.  In  certain  diseases  of  the  liver 
leucin  (and  tyrosin)  appear  in  the  urine,  which  may  be  interpreted  to  mean  that 
these  substances,  normally  produced  from  proteid  metabolism  in  the  tissues,  are 
not  normally  burned  but  accumulate  within  the  body,  and  are  excreted  (see 
below).  Proteid  on  chemical  treatment  may  yield  as  much  as  50  per  cent, 
of  leucin.  Since  leucin  contains  six  atoms  of  carbon  it  has  been  suggested 
by  Fr.  Miiller  that  this  substance  and  other  proteid  cleavage  products  con- 
taining six  carbon  atoms  may  be  the  mother  substances  of  the  sugar  produced 
in  diabetes.  Cohn2  asserts  that  feeding  leucin  to  rabbits  will  increase  the 
glycogen  in  their  livers,  but  this  increase  is  very  slight.  But  Halsey3  shows 
that  there  is  no  increase  in  sugar  in  the  urine  after  feeding  leucin  in  diabetes. 
It  may  be  that  a  sugar  radicle  in  proteid  may  be  the  mother-substance  of 
leucin  (see  p.  581). 

Leucin  and  tyrosin  are  found  in  yellow  atrophy  of  the  liver  both  in  the  urine  and  in 
the  liver  itself,  under  conditions  indicating  their  production  by  bacteria  and  their  non- 
combustion  after  production.  In  phosphorus-poisoning  and  acute  anaemia  leucin  and 
tyrosin  occur  in  the  urine,  but  apparently  without  good  ground  for  considering  them  of 
bacterial  oriuin. 

Leucin  crystallizes  in  characteristic  hall-shaped  crystals.  It  was  formerly  supposed  to 
be  amido-caproic  acid,  but  Schulze  4  has  shown  its  true  composition.  Inactive  leucin  con- 
-  3tfi  of  a  mixture  of  </-  and  /-leucin.  and  maybe  obtained  by  treating  conglutin  with 

1  Minkowski:   Archiv  fur  at/per.  Palhologie  unci  Pharmakotogie,  1886,  lid.  21,  S.  85. 

-'  Zeitschnft  fiir  physiologische  Chemie,  1899,  Bd.  28,  S.  211. 

nng8berichte  der  Oesellschqfi  zur  Befdrderung  der  gesammten  Naturwissenschaften  zu  Marburg, 
1899,  >.  102. 

1  Berichte  der  deutschen  chemischen  OeselUchaft,  1891,  Bd.  24,  S.  669  ;  also,  Gmelin:  Zeitxchrift 
fiir  physiologische  Chemie,  1893,  Bd.  18,  S.  38. 


THE   CHEMISTRY  OF   THE  ANIMAL  BODY.  541 

Ba(OH)2.  The  two  leucine  may  be  separated  by  fermentation  of  cZ-leucin  with  PeniciUium 
glaucum.  Cleavage  of  proteid  by  acids  and  by  putrefaction  seems  to  yield  cZ-leucin.1 
Cohn2  states  that  several  varieties  of  leucin  arise  in  tryptic  digestion. 

Caprylic,  C8H1602,  and  Capric,  C10H20O2,  Acids. — These  are  found  as 
glycerin  esters  in  milk-fat.     They  are  likewise  present  in  sweat  and  in  cheese. 

Palmitic,  C16H3202,  and  Stearic,  C18H3602,  Acids. — As  glycerin  esters 
these  two  acids  are  found  in  the  ordinary  fat  of  adipose  tissue,  and  in  the  fat 
of  milk.  The  acids  may  occur  in  the  feces,  and  are  found  combined  with 
calcium  in  adipocere  (p.  560).  Wool-fat  consists  of  the  cholesterin  esters  of 
these  acids. 

The  bile  contains  palmitic,  stearic,  and  oleic  acids,3  and  to  these  have  been 
attributed  its  very  slight  acid  reaction.4 

Compounds  of  the  Alcohol  Radicals  with  Nitrogen. 

Amines. — These  are  bodies  in  which  either  one,  two,  or  three  of  the  hydrogen  atoms 
in  ammonia  are  replaced  by  an  alcohol  radical,  and  are  termed  respectively  primary,  second- 
ary, and  tertiary  amines.  Methyl,  ethyl,  and  propyl  amine  bases  are  the  products  of  pro- 
teid putrefaction.     They  resemble  ammonia  in  their  basic  properties. 

Methylamine,  NH2(CH3). — This  is  found  in  herring-brine.  It  lias  the  fishy  smell 
noted  in  decaying  fish.  It  is  a  product  of  the  distillation  of  wood  and  of  animal  matter. 
Feeding  methylamine  hydrochloride  is  said  to  cause  the  appearance  of  methylated  urea  in 
a  rabbit's  urine  5  (analogous  to  the  formation  of  urea  from  ammonia  salts) : 
2HC1.NH2(CH3)  +  C02  =  OC(NHCH3)2  +  2HC1  +  H20. 
According  to  Sehiffer,6  the  body,  probably  through  intestinal  putrefaction,  has  the  power 
of  partially  converting  creatin  into  oxalic  acid,  ammonia,  carbonic  acid,  and  methylamine, 
which  last  is  finally  excreted  as  methylated  urea  in  the  urine. 

Ethylamine,  C2H5NH2,  when  fed  as  carbonate  appears  in  part  as  ethylated  urea  in  the 
urine.7 

Trimethylamine,  N(CH3)3. — Like  ethylamine,  this  is  found  in  herring-brine  and 
among  the  products  of  proteid  putrefaction  and  distillation.  In  the  putrefaction  of  meat 
the  first  ptomaine  appearing  is  cholin,  which  certainly  is  derived  from  lecithin  ;  the  cholin 
(see  p.  543)  gradually  disappears,  and  in  its  place  trimethylamine  may  be  detected.8 

Compounds  with  Cyanogen. 

The  radicle  NC —  forms  a  series  of  bodies  not  unlike  the  halogen  com- 
pounds. Owing  to  the  mobility  of  the  cyanogen  group,  Pfltiger9  has  sought 
to  attribute  the  properties  of  living  proteid  to  its  presence  in  ili«'  molecule, 
whereas  in  the  dead  proteid  of  the  blood-plasma,  for  example,  he  imagines  that 
the  nitrogen  is  contained  in  an  amido-  group.  When  the  cyanogen  radical 
occurs  in  a  compound  in  the  form  of  N==C —  the  body  is  called  a  nitril,  when 
in  the  form  of  C=N —  an  iso-nitril. 

Cyanogen  Gas,  NC  — CN. — A  very  poisonous  gas. 

1  Gmelin:  Zeitsehrift fiir physiologisehe  Chemie,  1893,  I'd.  18,  8.28. 

2  Ibid.,  1895,  Bd.  20,  S.  203.  3  Lassar-Cohn  :    Ibid.,  1891,  Bd.  19,  S.  571. 
4  Jolles:    Pfliiger's  Archiv,  1894,  Bd.  57,  S.  13. 

*  Sehin'er  :  ZeUsehrift  fur  physiologisehe  Chemie,  1880,  Bd.  -1,  S.  2  )■">.  6  L<>c  cit. 

T  Schmiedeberg :  Archiv  fiir  exper.  Pathologic  and  Pharmakologie,  1877,  I'>d.  8,  S.  5. 
8  Brieger:  Abstract  in  Jahresberichi  iiber  Thierehemie,  L885,  8.  101. 
s  Pfliiger's  Archiv,  1875,  Bd.  10,  S.  251. 


54:2  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

Hydrocyanic  Acid,  HON. — This  is  likewise  a  strong  poison.  Amygdalin  is  a  glucoside 
occurring  in  cherry-pits,  in  bitter  almonds,  etc.,  together  with  a  ferment  ealled  emulsin, 
which  hitter  hasthe  power  of  transforming  amygdalin  intodexfcrose,  benzaldehyde,  and  hydro- 
cyanic acid.  Bydrocyanic  acid,  therefore,  gives  its  taste  to  oil  of  bitter  almonds,  and  it 
may  likewise  be  detected  ill  cherry  brandy. 

Potassium  Cyanide,  KCN. — This  and  all  other  soluble  cyanides  arc  fatal  poisons. 

Acetonitril,  or  Methyl  Cyanide,  CHSCN. — This  and  its  higher  homologous  nitrils 
are  violent  poisons.  After  feeding  acetonitril  in  small  doses,  formic  acid  (see  p.  534)  and 
thiocyanic  acid  (see  below)  appear  in  the  urine,  the  thiocyanic  acid  being  a  synthetic  prod- 
uct of  the  ingested  cyanogen  radical,  and  the  HS —  group  of  decomposing  proteid.1  After 
feeding  higher  homologues  of  acetonitril  or  hydrocyanic  acid,  thiocyanide  likewise  appears 
in  the  urine.  Since  the  amount  of  thiocyanide  in  the  urine  is  normally  very  small,  there 
is  no  reason  for  believing  that  cyanogen  radicals  similar  to  those  described  above  are  ever, 
to  any  great  extent,  cleavage-products  of  proteid.8  Through  intravenous  injections  of 
sodium  sulphide,  and  especially  of  sodium  thiosulphate,  poisonous  cyanogen  compounds 
may  be  administered  much  beyond  the  dose  ordinarily  fatal:8 

NaCN  +  S02  <  |^aa  +  0  =  NCSNa  +  Na2S04. 

Cyanamide,  NC.NH2. — This  is  a  laboratory  decomposition-product  of  creatin,  but  does 
not  occur  in  the  body.  It  is  poisonous  when  administered.  When  boiled  with  dilute 
sulphuric  or  nitric  acids  it  is  converted  into  urea : 

NCNH,  +  H20  =  H2NCOXH2. 
It  is  to  be  remembered  that  creatin  in  the  body  is  not  converted  into  urea. 

Ammonium  Cyanate,  OCN(NH4). — Boiling  ammonium  cyanate  converts  it  into 
urea.  This  was  shown  by  Wohler  in  1828,  and  was  the  first  authoritative  laboratory 
production  of  a  body  characteristic  of  living  organisms: 

OCNiNH4)=OC(NH2)2. 
This  reaction  illustrates  Pfliiger's  idea  of  the  transformation  of  the  unstable  cyanogen  radical 
in  living  proteid  into  the  amido-  compound  in  the  dead  substance.     According  to  Hoppe- 
Seyler,  the  urea-formation  in  the  body  is  as  indicated  in  the  above  reaction,  but  that  no 
cyanic  acid  or  ammonium  cyanate  is  to  be  detected  on  account  of  their  extreme  instability. 

Potassium  Thiocyanide,  NCSK. — This  substance  is  usually  found  in  human  saliva  to 
the  extent  of  about  iU>]  per  cent.,  and  in  the  urine.  Since  it  contains  nitrogen  and  sul- 
phur its  original  source  must  be  from  proteid.  The  amount  in  the  urine  is  probably  wholly 
and  quantitatively  derived  from  that  in  the  saliva.4  If  thiocyanides  be  fed,  they  appear 
quickly  in  the  urine  without  change.  Thiocyanides  are  less  poisonous  than  the  simple 
cyanides  (see  discussion  under  Acetonitril  above).  Thiocyanides  give  a  red  color  with 
ferric  chloride  in  acid  solution. 

Diatomic  Alcohol  Radicals. 
Thus  far  onlv  derivatives  of  monatomic  radicals  have  been  discussed ;  next 
in  order  follow  diatomic  alcohol  radicals,  represented  by  the  formula  C„H2I1,  and 
including  the  bodies  ethylene,  H2C  —  CH2,  propylene,  CH3 — HC  =  CH2,  etc. 
This  set  of  hydrocarbons  is  called  the  olefines.  The  first  series  of  compounds 
which  are  of  physiological  interest  are  the  amines  of  the  olefines. 

Amines  of  the  Olefines. 
These  include  the  group  of  ptomames — basic  substances  which  are  formed 
from  proteid  through  bacterial  putrefaction.     Those  which  are  poisonous  are 

1  Lang:  Arrhiv  fur  exper.  Pathologic  wad  Pharmakologie,  1894,  P>d.  34,  S.  247. 

2  Op.  cit.,  S.  256. 

■  Lang:  Archiv  fur  exper.  Pathologic  und  Pharmakologie,  1895,  Bd.  36,  S.  75. 
*Gscheidlen:  Pfliigei's  Archiv,  1S77,  Bd.  14,  8.  411. 


THE   CHEMISTRY   OF   THE   ANIMAL    BODY.  543 

called  toxines.  These  bodies  are  diamines  of  the  olefmes,  and  have  been 
investigated  especially  by  Brieger.1 

Tetramethylene-diamin,  or  Putrescin,  H2N.CH2.CH2.CH,.CH, Nil,.— This  com- 
pound is  found  in  putrefying  proteid,  and  has  been  detected  in  the  urine  and  feces  in 
cystitis. 

Pentamethylene-diamin,  or  Cadaverin,  H,N.C5TI10.NH2.— This  is  found  with 
putrescine  wherever  produced.  They  are  both  found  in  cultivations  of  Koch's  cholera  bacil- 
lus and  in  cholera  feces.  In  cystitis  they  are  a  result  of  special  infection  of  the  intestinal 
tract,  are  principally  excreted  in  the  feces,  but  are  partially  absorbed,  and  prevent,  perhaps 
through  chemical  union,  the  burning  of  cystein  normally  produced.2  Diamines  are  not 
normally  present  in  the  urine. 

Neuridin.  and  Saprin. — These  are  isomers  of  cadaverin  and  are  produced  by  the  same 
putrefactive  processes. 

Cholin. — This  is  trimethyl  oxyethyl  ammonium  hydroxide, 

(CH3)3-N<CH2CHOH 

and  has  its  source  in  lecithin  decomposition,  and  putrefaction  (see  p.  559).  Cholin  has 
been  found  in  the  cerebrospinal  fluid  in  cases  of  general  paralysis  in  the  insane,  and  is 
regarded  as  the  effective  poison.3 

Muscarin,  or  Oxycholin. — This  is  a  violent  heart-poison,  and  may  be  obtained  by 
treating  cholin  with  nitric  acid. 

Neurin. — This  is  trimethyl-vinyl  ammonium  hydroxide,  (CH3)3  ~  N  <  p jj  _  q jj 

and  is  derived  from  lecithin.  It  may  be  considered  as  derived  from  cholin,  with  the 
elimination  of  a  molecule  of  water,  and  it  has  been  shown  that  bacteria  make  this  conver- 
sion. It  is  a  powerful  poison.  After  feeding  lecithin  and  occluding  the  intestinal  canal, 
cholin  and  neurit]  have  been  found  within  the  intestinal  contents.4 

Derivatives  of  Diatomic  Alcohols. 

Taurin,  or  Amido-ethyl  Sulphonic  Acid,  H2N.CH2.CH2.S03H.— This 
lias  been  detected  in  muscle,5  in  the  spleen,  and  in  the  suprarenal  capsules. 
It  is  likewise  a  usual  constituent  of  the  human  bile  in  combination  with 
cholic  acid,  the  salt  present  being  known  as  sodium  tauroeholate.  Taurin 
is  of  proteid  origin  as  is  shown  by  its  nitrogen  and  sulphur  content.  Little 
is  known  regarding  its  fate  in  the  body,  except  as  is  indicated  through  the 
behavior  of  its  sulphur  atom  (see  p.  507). 

The  Biliary  Salts. — Taurin  and  glycocoll  are  found  in  the  bile  of  cattle  in 
combination  with  cholic  acid  (C^H^O^.  In  human  bile,  according  to  Lassar- 
Cohn,"  there  is  more  fellic  acid  (C^H^OJ  present  than  cholic,  and  there  is 
likewise  present  some  choleic  acid,  (C^H^C^).  These  acids  arc  of  similar  chemi- 
cal structure,  though  what  the  structure  is,  is  unknown.  Still  other  acids 
occur  in  the  bile  of  pigs,  geese,  etc.  Taurin  and  glycocoll  form  compounds 
with  these  acids,  the  sodium  salts  of  which  usually  make  up  the  major  part  of 

1  Abstract,  Jahresbcricht  iiber  I'hierchemie,  1885.  S.  101. 

*  Baum.inn  und  Udranszky  :  Zeitschrift  fur  phygiologische  Chemie,  1889,  Bd.  13,8.  562,  and 
1891,  Bd.  15,  8.  77. 

3  Mott  and  Halliburton  :  Journal  of  Physiology,  1899,  vol.  xxiv.  p.  ix. 

*  Nesbitt,  B. :  American  Journal  of  Physiology,  1899,  vol.  ii.  p.  viii. 

5  Keed,  Kunkenberg,  and  Wagner:  Zeitschrift  fiir  Biologic,  1885,  Bd.  21,  B.  30. 

6  Z>  itschrift  fiir  physiologische  Chemie,  1894,  Bd.  19,  S.  570. 


544  AN  AMERICAN    TEXT- HOOK    OF    1'HYSloLOGY. 

the  solids  of  the  bile.  It  has  been  shown  that  glycocoll  and  taurin  are  found 
in  various  parts  of  the  body.  Cholic,  fellic,  etc.  acids  are  only  found  as  products 
of  hepatic  activity.  In  a  dog  with  a  biliary  fistula  the  solids  of  the  bile  increase 
on  feeding  much  meat,  but  the  hourly  record  of  the  solids  compared  with 
the  nitrogen  in  the  urine  shows  that  the  great  production  of  biliary  salts  con- 
tinues after  the  nitrogen  in  the  urine  has  beguu  to  decrease.1  The  experiments 
of  Feder2  have  shown  that  the  greater  part  of  the  nitrogen  in  proteid  eaten  by 
a  dog  leaves  the  body  within  the  first  fourteen  hours,  whereas  the  excretion  of 
the  non-nitrogenous  moiety  is  more  evenly  distributed  over  twenty-four  hours. 
It  may  be  fairly  concluded  that  cholic  and  fellic  acids  are  produced  from  the 
non-nitrogenous  portion,  or  from  sugar  or  fat.'  Furthermore  Tappeiner  '  has 
6ho\\^i  that  cholic  acid  on  oxidation  yields  fatty  acids.  A  synthesis  may  there- 
fore be  effected  in  the  liver  bit  ween  the  non-nitrogenous  cholic  acid  formed  in 
the  liver  from  fat  or  materials  convertible  into  fat,  and  glycocoll  and  taurin 
formed  from  proteids,  whether  the  latter  be  produced  in  the  liver  or  brought  to 
it  from  tlu1  tissues  by  the  blood.  That  the  liver  is  the  place  for  the  synthesis 
is  shown  by  the  fact  that  the  biliary  salts  do  not  collect  in  the  body  after  extir- 
pation of  the  liver. 

The  biliary  salts  in  part  may  be  absorbed  by  the  intestine,  and  a  part  of 
these  absorbed  salts  may  be  again  excreted  through  the  bile,  forming  a  circu- 
lation of  the  bile  salts.  In  the  intestine  either  the  acid  of  the  gastric  juice 
or  bacteria  may  split  up  the  biliary  salt  through  hydrolysis: 

C26H,3M\+  H20  -  C2H6N02  +  C.^H^O,. 

Glycocholic  acid.  Glycocoll.  Cholic  acid. 

Taurin  and  glycocoll  may  be  absorbed,  while  cholic  acid  is  precipitated  if  in 
an  acid  medium,  but  may  be  dissolved  and  absorbed  in  an  alkaline  intestine. 
Hence  cholic  acid,  fellic  acid,  etc.,  may  often  be  found  in  the  feces  in  small 
amount-.  .Meconium,  that  is.  the  fecal  matter  of  the  fetus,  contains  quantities 
of  the  biliary  salts,  but  unaltered,  since  putrefaction  is  absent  in  the  fetus. 
Kiihne  has  described  dyslysin  as  a  putrefactive  product  of  cholic  acid,  but  its 
existence  is  denied  by  Hoppe-Seyler  and  Yoit.  In  icterus  (jaundice),  a  con- 
dition in  which  the  biliary  salts  return  to  the  blood  from  the  liver,  they  are 
burned  in  the  body,  sometimes  so  completely  that  none  appear  in  the  urine. 
They  have  the  power  of  dissolving  haemoglobin  from  the  blood-corpuscles,  and 
in  consequence  the  urine  may  be  highly  colored,  perhaps  from  bilirubin.5 

The  biliary  salts  have  the  power  of  dissolving  the  more  insoluble  fatty 
acids  and  soaps  produced  from  the  action  of  steapsin  on  fats.1' 

Pettenkofer,  experimenting  once  on  the  conversion  of  sugar  into  fat.  warmed  together 
cane-sugar,  bile,  and  concentrated  sulphuric  acid.  He  obtained  no  fat,  but  a  strong  violet 
coloration.  This  is  "  Pettenkofer's  test"  for  biliary  acids  (cholic  acid,  fellic  acid,  etc.). 
This  coloration  is  likewise  given  by  proteid,  oleic  acid,  and  other  bodies.     The  test  of'Neu- 

1  Yoit :  Zeitschrift  fur  Biologie,  1894,  Bd.  30,  S.  545.  2  Ibid.,  1881,  Bd.  15,  S.  531. 

5  Yoit,  Op.  ril.,  S.  556.  4  Zeitschrift  fur  Biologie,  1876,  Bd.  12,  S.  60. 

5  Hoppe-Seyler:  Physiohgische  Chemie,  1877,  S.  476. 

6  Moore  and  Rockwood  :  Journal  of  Physiology,  1897,  vol.  xxi.  p.  58. 


THE   CHEMISTRY  OE   THE  ANIMAL   BODY.  545 

konmi  is  a  modification  of  this.  Here  a  drop  of  a  substance  containing  biliary  acids  is 
placed  on  a  small  white  porcelain  cover,  with  a  drop  id'  dilute  cane-sugar  solution,  and  one 
of  dilute  sulphuric  acid;  the  mixture  is  then  very  carefully  evaporated  over  a  flame  and 
leaves  a  brilliant  violet  stain. 

Oxy-  Fatty  Acids,  Lactic-acid  Group. 

These  are  diatomic  monobasic  acids  of  the  glycols.  A  glycol  is  a  diatomic 
alcohol.     The  oxy-  fatty  acids  have  the  general  formula  CnH2I103,  and  include  : 

Carbonic  acid,  CH203.  Oxy-butyric  acid,  C4H803. 

Glycollic  acid,  C2IT403.  Oxy-valerianic  acid,  C5H10O3. 

Lactic  acid,  C3H603.  etc. 

Carbonic  Acid,  or  Oxy-formic  Acid,  HO.CO.OH. — This  is,  in  reality, 
a  dibasic  acid  on  account  of  the  symmetric  structure  of  the  two  — OH  radicals. 
It  has  already  been  considered. 

Lactic  Acids,  or  Oxy-propionic  Acids. — Of  these  there  are  two  isomeres, 
which  vary  in  the  position  of  their  — OH  group,  the  a-  and  ft-  lactic  acids. 
Physiology  is  concerned  only  with  the  first. 

a-Lactic  Acid,  or  Ethidene  Lactic  Acid,  CH3.CHOH.COOH. — This 
is  called  fermentation  lactic  acid,  being  a  product  of  the  fermentation  of  carbo- 
hydrates (see  p.  539)  : 

C6H1206  =  2C3H603- 

On  lactic  fermentation  of  milk-sugar  depends  the  souring  of  milk.  This  fer- 
mentation does  not  take  place  in  the  presence  of  sufficiently  acid  gastric  juice, 
but  maybe  more  active  in  the  alkaline  intestine.  It  has  been  noticed  that  the 
fecal  excrements  after  a  carbohydrate  diet  react  acid,  after  proteid  diet  alkaline. 
The  acid  reaction  is  due  chiefly  if  not  wholly  to  acetic  acid,  since  lactic  acid, 
being  the  stronger  acid,  is  first  neutralized  by  the  intestinal  alkali.  Lactic 
acid,  when  absorbed,  is  completely  burned  in  the  body.  Lactic-acid  fermenta- 
tion between  the  teeth  dissolves  the  enamel,  and  gives  bacteria  access  to  the 
interior.  The  fermentation  lactic  acid  is  inactive  to  polarized  light,  and,  since 
it  has  in  its  formula  an  asymmetric  carbon  atom,'  it  is  necessary  to  assume 
that  it  consists  of  an  equal  mixture  of  right  and  left  ethidene  lactic  acid.    On 

1  An  asymmetric  carbon  atom  is  one  in  which  the  four  atoms,  or  groups  of  atoms,  united  to 

CHa 
I 
it  are  all  different.     In  lactic  acid  we  find  the  following  grouping,  II — C — Oil.     The  central 

COOK 

carbon  represents  the  asymmetric  atom.     Such  an  arrangement  is  always  optically  active.     <  me 
is  able  to  conceive  the  arrangement  of  the  atoms  in  space,  according  to  the  above  grouping,  >>r 
CI  I, 

as  follows:  HO— C— H.     This  latter  represents  a  different  configuration.     The  two  arrange- 

1 

coon 

ments  are  optically  antagonistic.  A  mixture  of  the  two  is  optically  inactive.  The  reader  is 
referred  to  a  text-book  on  general  chemistry  for  the  suggestive  illustrations  of  the  tetrahedral 
space  pictures. 

Vol.  I.— 35 


546  AN    AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

standing  with  PeniciUium  glaucurn  the  left  lactic  acid  is  destroyed  more  freely 
than  is  the  right,  and  the  solution  rotates  polarized  light  to  the  right.1 

The  right  ethidene  lactic  acid,  called  also  sarco-  or  para-lactic  acid,  is  that 
which  is  found  in  muscle,  blood,  in  various  blood-glands,  in  the  pericardial 
fluid,  and  in  the  aqueous  humor.  Likewise  it  is  found  in  the  urine  after 
strenuous  physical  effort,  after  CO-poisoning,  in  yellow  atrophy  of  the  liver, 
in  phosphorus-poisoning,  in  trichinosis,  and  in  birds  (geese  and  ducks)  after 
the  liver  has  been  extirpated,  and  it  is  found  in  increased  quantities  in  the 
blood  and  in  all  the  organs  of  animals  poisoned  with  arsenic.-  It  is  some- 
times present  in  diabetic  urine.  Para-lactic  acid  is  a  normal  constituent  of  the 
blood  and  increases  in  amount  after  work  or  tetanus.  It  accumulates  in  the 
dying  muscle  {rigor  mortis),  causing  the  formation  of  KH2P04,  which  gives 
the  acid  reaction  and  causes  coagulation.3  Some  believe  that  free  lactic  acid 
itself  is  present  and  aids  in  the  coagulation.  Regarding  its  origin,  it  has  been 
shown  that  it  increases  in  amount  in  the  dying  muscle  without  simultaneous 
decrease  in  the  amount  of  glycogen.4  It  has  also  been  shown  that  the  large 
increase  of  lactic  acid  in  the  extirpated  liver  is  only  due  to  the  production  of 
fermentation  lactic  acid  from  glycogen.'  On  extirpation  of  the  liver  in  geese,6 
ammonia  and  para-lactic  acid  replace  the  customary  uric  acid  in  the  excreta, 
and  previous  ingestion  of  carbohydrates  or  of  urea  will  not  increase  the 
amount  of  para-lactic  acid.  The  lactic  acid  excreted  is  proportional  in 
amount  to  the  proteid  destroyed  and  to  the  ammonia  present.  It  may  fairly 
be  concluded  that  it  always  owes  its  origin  to  proteid. 

Hoppe-Seyler '  says  that  lactic  acid  appears  in  the  urine  only  when  there  is  insufficient 
oxidation  in  the  body,  and  attributes  its  derivation  to  the  decomposition  of  glycogen.  In 
( '( ^-poisoning  Araki"  finds  as  much  as  2  per  cent,  of  lactic  acid  (reckoned  as  zinc  lactate  in 
a  rabbit's  urine.  Minkowski,9  on  the  other  hand,  denies  the  insufficient-oxidation  theory, 
and  maintains  that  the  destruction  of  lactic  acid  depends  on  a  specific  property  of  the 
liver,  the  normal  action  being  either  destruction  in  the  liver  itself  or  in  other  organs 
through  the  medium  t>\'  a  substance  (enzyme?)  produced  in  the  liver. 

One  may  interpret  Araki's  experiment  as  showing  that  considerable  quantities  of  lactic 
acid  arc  constantly  produced  in  metabolism,  but  are  normally  swept  away  and  burned;  the 
CO-poisoning  would  prevent  the  normal  combustion.  The  accumulation  in  muscle  after 
stoppage  el'  the  blood  current  [rigor  mortis)  would  then  be  only  a  continuation  of  the  nor- 
mal process  of  decomposition. 

Cyste'in,  a-Amido-a-thiopropionic  Acid. — This  substance  has  the  formula 

1  Berichte  der  deulschen  chemischen  Gesellschaft,  Bd.  L6,  S.  2720. 
-'  Morisbima :   Archiv  fiir  exper.  Pathologic  umd  Pharma/eologie,  1899,  Bd.  43,  S.  217. 
3  Astaschewski  :  Zeitsehrifl  fur  physiologische  Chemie,  1880,  Bd.  4,  S.  403;  [risawa,  Ibid.,  1893, 
Bd.  17,  S.  351. 

'Boehm:    P  Irchiv,  1880,  Bd.  23,  S.  44.  5  Morisbima :  Loe.  cit. 

,;  Minkowski:  Archiv  fur  exper.  Pathologic  mul  Pharmacologic,  1S86,  Bd.  21,  S.  41. 

7  /■  ttschrift  zu  /■'.  Virchovfs  70.  Geburtstag. 

-  Zeitsehrifl  fur  physiologische  Chemie,  1894,  Bd.  19,  S.  426. 

s  hoc.  cit.,  and  Archiv  fiir  exper.  Pathologic  und  Pharmakologie,  1893,  Bd.  31,  S.  214. 


THE   CHEMISTRY   OF   THE  AS IMA  L   BODY.  547 

NH2 
CH3 — C — COOH.     It  is  a  product  of  proteid  metabolism  and  is  normally 

SH 

destroyed  in  the  body.  On  the  introduction  of  a  halogen  derivative  of  benzol 
into  the  body,  compounds  are  formed  with  cyste'in,  called  mercapturic  acids, 
which  appear  in  the  urine  : 

NH2  NH2 

CH3-C— COOH  +  C,H5Br  +  O  =  CH3— C— COOH  +  H20. 

I  I 

8H  SC6H4Br. 

Broraophenyl-mereapturic  acid. 

This  proves  that  cystei'n  (like  glycocoll,  for  example)  is  at  least  an  intermediary 
and  possibly  a  primary  product  of  proteid  metabolism,  [f  cyste'in  be  fed,  the 
greater  part  (two-thirds)  of  the  sulphur  appears  in  the  urine  as  sulphuric  acid, 
the  rest  as  neutral  sulphur.  Thiolactic  acid  has  been  found1  as  a  decomposition 
product  of  horn.  Baumann 2  demonstrates  the  reduction  of  cyste'in  to  thiolactic 
acid,  shows  that  the  latter  yields  an  odor  of  ethyl  sulphide  on  evaporation, 
and  asks  if  thiolactic  acid  be  not  the  mother  substance  of  Abel's  compound 
(see  p.  507) : 

NH2 
CH3— C— COOH  +  H2  =  CH3CH(SH)COOH  +  NH3. 

Thiolactic  acid. 

SH 

Cyste'in  itself  is  never  directly  detected  in  the  urine  or  in  the  body. 

Cystin,  Dithio-diamido-ethidene  Lactic  Acid. — Cyste'in  is  converted  by 
atmospheric  oxygen  into  cystin  : 

NH, 


2CH  —  C— COOH  +  20  = 


CH3— CSNH2— COOH 


CH3— CSNH— COOH 


S'I  Cystin. 

Cystin  is  very  insoluble  in  water.  In  particular  cases  it  appears  in  considerable 
quantities  as  a  urinary  sediment,  still  more  rarely  as  a  stone  in  the  bladder 
(see  p.  543).  It  has  been  detected  in  the  normal  livers  of  horses.'  It  is 
Iaevo-  rotatory. 

It  is  reported  *  that  bodies  having  the  composition  ('     S      II  ithio-  acids,  meivaptans) 
may  form   sulphuric   acid,  while   most  of  those   having   the   composition      0 — S — C 
(ethyl  sulphide)  are  not  oxidized  in  the  body. 

1  Suter:  ZeUaehrift  fur  physiologische  Chemie,  1895,  Bd.  20,  S,  564. 

2  Baumann:   Tbid.,  1895,  Bd,  20,  6.  583. 

3  Drechsel  :  Zeitsehrift  fur  Biologie,  1897,  Bd.  33,  S.  B5. 

*  W.  .J.  Smith  :   Pfliiger's  Archiv,  1894,  Bd.  -V),  S.  542,  and  1894,  Bd.  57,  S.  H8. 


548  AN   AMERICAN    TEXT- BOOK    OE  PHYSIOLOGY. 

,9-Oxybutyric  Acid,  CH3CHOHCH2COOH. — A  lsevo-rotatory  acid  (see 
p.  539). 

Amido-  Derivatives  of  Carbonic  Acid. 
OC'<OH-  OC<OH-  0C<NH:- 

Carbonic  acid.  Carbamic  acid.  Carbamide. 

Carbamic  Acid. — This  is  not  known  free,  but  its  calcium  .salts  have  been 
found,  especially  in  herbivorous  urine,  and  its  presence  in  the  blood  as  ammo- 
nium carbamate  is  maintained.1  The  latter  has  been  obtained  by  Drechsel2  by 
oxidizing  glyeocoll  and  leuein  in  ammoniacal  solution,  and  he  has  converted  it 
into  urea  by  electroly.sis.  From  these  facts  he  concludes  that  ammonium  car- 
bamate is  the  antecedent  of  urea.  It  must,  however,  be  remembered  that 
ammonium  carbamate  is  very  readily  decomposable,  and  has  never  been 
directly  detected  in  the  blood. 

Ammonium  carbamate  is  formed  by  the  direct  union  of  ammonia  with  car- 
bonic oxide  in  their  nascent  states,  and  is  therefore  found  in  commercial  ammo- 
nium carbonate  and  as  the  product  of  the  oxidation  of  the  amido-  compounds 
above  mentioned  : 

2XH3  +  C02=OC<g£f^ 

Water  converts  it  into  ammonium  carbonate  : 

oc<Snh4+h*0=oc<£nh;- 

Carbamide,  or  Urea,  OC(NH2)2. — This  is  the  principal  end-product  of  the 
nitrogenous  portion  of  proteid  in  all  mammals,  being  found  in  considerable 
concentration  in  the  urine.  Schondorff3  finds  in  the  blood,  liver,  spleen, 
pancreas,  and  brain  about  0.12  per  cent,  of  urea,  while  muscle  contains  0.09 
per  cent.,  the  heart  0.17  per  cent.,  and  the  kidney  0.(57  per  cent.  In  uraemia 
it  may  collect  in  all  tissues  of  the  body,  and  may  then  be  excreted  in  slight 
amount  by  the  gastric  and  intestinal  juices.  It  is  given  off  in  profuse  sweat- 
ing, though  only  in  small  proportion  to  that  lost  in  the  urine. 

Preparation. — -(1)  Like  other  amides,  by  heating  ammonium  carbonate; 
further,  by  the  electrolysis  of,  or  by  heating,  ammonium  carbamate: 

OC<ONH   =  OC<XH2  +  2H2°- 

ocx™^  =  oc<™;  +  h2o. 

(2)  Through  the  union  of  ammonia  with  carbonyl  chloride: 

1  Drechsel:  Lvdvng'a  Arbeiten,  1875,  S.  172;  Drechsel  und  Abel,  Archiv  fur  Physiologic,  1891, 
S.  242. 

*  Loc.  cit.  *  Prfiiger's  Archiv,  1899,  Bd.  74,  S.  307. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  549 

OCCl2  +  2NH3  =  OC(NH3)2  +  2HC1. 

(3)  By  evaporating  an  aqueous  solution  of  ammonium  cyanate : 

O:0:N.NH4  =  OC(NH2)2. 

This  was  Wohler's  notable  preparation  in  1828  of  an  "organic"  compound, 
a  product  of  life,  without  the  aid  of  a  "  vital  force." 

(4)  From  proteid,  through  hydrolytic  cleavage1  (see  p.  551).  This  origin 
has  not  as  yet  been  confirmed. 

Properties. — Urea  is  a  weak  base,  of  great  stability  when  within  the  alka- 
line fluids  and  tissues  of  the  body.  It  is  soluble  in  water  in  all  proportions, 
very  soluble  in  hot,  less  so  in  cold  alcohol,  whence  it  crystallizes  in  needle-like 
forms.  It  melts  at  132°  and  recrystallizes  on  cooling.  Heated  higher  it  is 
converted  into  biuret,  a  substance  which  gives  a  violet  color  with  dilute  cupric 
sulphate  in  a  sodium-hydrate  solution  (called  the  biuret  reaction)  : 

NH 
NH         OC<       2 

20C<nhI  -  oc<NH  +  NH* 

NH2 

Heating  urea  with  water  over  100°  in  sealed  tubes,  boiling  it  with  alkalies 
or  acids,  bacterial  action  (see  p.  512),  all  convert  it  through  hydrolysis  into 
carbonic  oxide  and  ammonia.  Such  decompositiou  may  take  place  in  the 
stomach  in  uraemia.2  Hypobromite  of  sodium  in  the  presence  of  alkali  acts 
to  break  up  urea,  thus  : 

OC(NH2)2  +  3NaBrO  =  C02  +  2H20  +  2N  +  3NaBr. 

The  alkali  present  absorbs  the  C02,  and  the  volumes  of  N  afford  a  measure  for  the 
amount  of  urea  present  (method  of  Hufner,  apparatus  by  Doremus). 

Urea  combines  with  nitric  acid  to  form  urea  nitrate,  OC(NH2)2.HN03, 
which  is  insoluble  in  nitric  acid.  Urea  oxalate,  which  is  formed  in  similar 
manner  by  the  combination  of  urea  with  oxalic  acid,  is  insoluble  in  water. 
Many  combinations  with  metallic  salts  have  been  prepared,  of  which  one  with 
mercuric  nitrate,  of  uncertain  formula,  is  the  basis  of  Liebig's  method  of  titra- 
tion for  urea. 

Urea  in  the  Body. — This  subject  has  been  discussed  under  Nutrition. 
It  can  be  considered  here  only  briefly.  When  urea  is  fed  it  is  rapidly  excreted 
in  the  urine.  The  excreted  nitrogen  of  proteid  appears  in  mammalia  in  greater 
part  as  urea.  Amido-  products  of  proteid  decompositiou,  glycocoll,  leuciu, 
aspartic  acid,  uric  acid,  when  fed  are  converted  by  the  body  into  urea.  So  like- 
wise are  ammonium  carbonate,  lactate,  and  tartrate  Ammonium  chloride,  on 
account  of  the  strong  acid  radical,  passes  through  carnivora  unchanged,  but  in 
herbivora,  the  blood  of  which  is  more  strongly  alkaline,  a  certain  part  of  the 
ammonia  is  converted  first  into  carbonate  and  then  into  urea.  This  conversion 
of  ammonium  carbonate  into  urea  is  of  striking  interest.  Artificial  irrigation 
of  a  liver  with  blood  containing  ammonium  carbonate  increases  the  urea  in 

1  Drcclis.-l  :  Arehiv  fur  Physiologic,  1891,8.261. 

2  Voit:  Zeilschrifl  fiir  Biologie,  1868,  Bd.  1,  S.  150. 


550  AN   AMERICAN    TEXT- BOOK    OF   PHYSIOLOGY. 

the  blood,  while  similar  treatment  of  muscle  or  kidney  shows  no  such  results.1 
In  other  experiments  it  has  been  shown  that  ammonium  salts  appear  in  the 
urine  alter  feeding  acids  to  carnivore,  and  that  in  disease  in  which  acids  are 
produced  (lactic,  aceto-acetic,  oxybutyric  acids)  ammonia  accompanying  them 
is  found  in  the  urine,  in  all  eases  representing  that  ordinarily  converted  into 
urea.  In  disease  of  the  liver  (cirrhosis,  phosphorus-poisoning)  ammonia  is 
found  in  the  urine  above  the  normal.  If  the  liver  be  excluded  from  the 
dog's  circulation  by  Eck's  fistula,  ammonium  salts  accumulate  in  the  blood. 
If  an  amido  body  like  ijlycocoll  be  i'vA  to  such  a  dogr,  ammonium  salts 
rapidly  accumulate,  which  indicates  the  normal  fate  of  glycocoll.2  .Amido 
acid-,  such  as  glycocoll,  leuein,  etc.,  which  arc  cleavage  products  of  proteids, 
and  which  are  known  to  burn  to  urea,  are  nevertheless  highly  resistant  to 
strong  chemical  reagents,  either  alkalies  or  acids.  Lewi's  3  work  indicates 
that  a  ferment  present  in  the  liver  (and  perhaps  elsewhere)  may  convert  these 
stable  compounds  into  others  in  which  the  nitrogen  is  less  (irmly  combined, 
which  may  in  turn  be  converted  into  urea.  Admitting  the  fact  that  ammonium 
carbonate  (and  carbamate  likewise)  may  be  converted  into  urea  by  the  liver, 
there  is  no  ground  for  believing  that  this  is  the  normal  process  for  the  produc- 
tion of  the  whole  amount  of  urea,  nor  is  there  at  present  any  measure  of  the 
amount  of  ammonium-salts  produced  in  the  body.  The  liver  may  be  very 
completely  destroyed  by  disease,  and  large  quantities  of  urea  still  be  excreted.4 
In  geese  extirpation  of  the  liver  has  no  effect  on  the  urea  excreted,  therefore  in 
geese  it  is  formed  elsewhere.5  For  aught  that  is  known,  therefore,  urea  may 
be  formed  in  other  organs  than  the  liver,  and  it  is  not  at  all  improbable  that 
it  is  formed  in  all  organs  where  proteid  decomposition  is  progressing.  The 
greater  part  of  urea  from  proteid  is  eliminated  in  the  dog  fourteen  hours  after 
his  meal  (see  p.  544). 

Guanidin,  HN:C<Cmtt".  This  is  the  imide  of  urea,  and  lias  been  obtained  by  the 
oxidation  of  guanin.  It  unites  with  alcohol  and  acid  radicals — forming,  for  example, 
methyl  guanidin,   HNC  <C  vii'Jut  •  au,l  guanidin  acetic  acid,  HN  <C  Kiihxj  POOTT 

Creatin,  or  Methyl  Guanidin  Acetic  Acid,  HXO  <  ^//-iVr  \nxj  POOTT 

(  Veatin  is  a  product  of  proteid  decomposition  and  found  in  muscle  to  the  ex- 
tent of  0.3  per  cent.,  in  traces  in  the  blood,  and  in  varying  amounts  in  the 
urine.  It  is  the  principal  constituent  of  meat-extracts  (Liobig's).  Creatin 
may  be  formed  synthetically  by  the  union  of  cyanamide  with  sarcosin,  and  it 
may  be  broken  up  into  these  constituents  by  boiling  with  barium  hydrate,  but 
the  cyanamide  is  Immediately  converted  into  urea  through  the  addition  of 
water  : 

1  Von  Schroeder  :   Archiv  fur  exper.  Pathologie  mi, I  Phnrmakohigic,  1882,  Bd.  15,  S.  3(i4, 
-  Salaskin,  8.  :  Zeitschriftfiir  physiologische  Chemie,  L898,  Bd.  25,  S.  449. 
8  Zeit&chrift  Jur  physiologische  Chemie,  L898,  Bd.  25,  S  511. 
1  Marfort:   Archiv  fur  exper.  Pathologie  mi, I  Pharmakokgie,  1894,  Bd.  33  S.  71. 
Minowski:   Ibid.,  1886,  Bd.  21,  8.62. 


THE   CHEMISTRY  OF   THE  ANIMAL    BODY.  551 

H2X.CX  +  HX(CH3)CH2COOH  =  HN:C <  ™J , ,  (  TI  roOH 

Cyanamide.  Sarcosin.  Creatin. 

Creatin,  however,  is  not  converted  into  una  in  the  body  if  fed,  1  mt  is  ex- 
creted in  the  urine  as  creatinin.1  The  amount  of  creatinin  found  in  the  urine 
corresponds  normally  to  the  amount  of  creatin  contained  in  the  meat  food  ;  in 
starvation  urine  it  is  proportional  in  amount  to  the  proteid  (muscle)  destroyed, 
being  present  even  on  the  thirtieth  day  (experiment  on  Succi2);  and  it  is 
present  only  in  traces,  or  not  at  all,  in  the  urine  of  milk-fed  children  (ereatin- 
free  food).  In  convalescence  creatin  is  said  to  be  retained,  possibly  for  the 
building  of  new  muscle.3  There  is  no  reason  for  believing  that  much  creatin 
is  ever  formed  in  the  body. 

Creatin  gives  its  flavor  to  meat.  If  gently  heated  it  gives  the  odor  of  roasting  beef. 
Creatinin  in  the  urine  reduces  alkaline  solutions  of  copper  salts  (eare  must  be  taken,  there- 
fore, in  making  the  sugar  test  after  using  meat  extracts).  The  action  of  creatin  is  simply  that. 
of  a  pleasant-tasting,  pleasant-smelling  substance,  which  prepares  the  stomach  for  food 
but  has  no  nourishing  value  per  se.     It  is  considered  by  some  to  be  a  nerve-stimulant. 

Creatinin,  or  Glycolyl  Methyl  Guanidin. — Heating  creatin  with  acids 
changes    it    into    creatinin    with    loss  of    water,    and     having    the    formula 

NH— CO 
HN:C^  .     Warming   to  60°  with  phosphoric  acid    causes  this 

\N(CH3)CH2 
conversion.  In  like  manner  when  the  kidney  prepares  an  acid  urine,  creatin 
becomes  creatinin  :  if  the  acid  reaction  be  effaced  through  feeding  alkaline 
salts  the  creatin  is  excreted  unchanged.4  Creatinin  with  chloride  of  zinc 
forms  a  characteristic  very  insoluble  white  powder  of  creatinin  zinc  chloride, 
(C4H7X30)2.ZnCl2. 

Lysatin,  C6H13N202,  and  Lysatinin,  C6HUN3C)2. — These  substance-  are 
obtained,  like  lysin  (sec  below),  from  the  hydrolytic  cleavage  of  proteid,  as  for 
example  from  casein  or  conglutin  heated  with  hydrochloric  acid  and  zinc 
chloride;  they  are  probably  likewise  produced  in  trypsin  digestion.5 

According  to  Drechsel6  they  are  homologues  of  creatin  and  creatinin,  and 
therefore  should  yield  urea  on  heating  with  barium  hydroxide.  This  is 
Drechsel's  method  of  direct  production  of  urea  from  proteid  by  hydrolytic 
cleavage. 

Diamido-  Fatty  Acids. — Of  these  four  have  been  described: 

Diamido-acetic  Acid,  CII(XII.2)2COOII. — This  was  found  by  Drechsel1  among  other 
compounds  after  heating  casein  in  scaled  tubes  with  concentrated  hydrochloric  acid  at  I  I"  • 
Diamido-proprionic  acid  has  not  been  Pound  in  the  body. 

1  Voit:  Zeitschrift  fur  Biologic,  L868,  Bd.  4,  S  114. 

2  Luciani :  Das  Hungern,  Leipzig,  1H90,  S.  144. 

;i  Von  Noorden  :  Pathologie  des  Stoffwechsels,  1893,  S.  Ki9. 
*Voit:  Zeitschrift  fur  Biologie,  1868,  Bd.  I,  S.  loO. 

5  See  Drechsel,  and  his  pupils  Fisher,  Siegfried,  and  Hedia  :  Arehivjur  Physiologie,  1891,  S. 
248  et  seq. 

6  (Jp.  cit.,  S.  261.  7  Abstract  in  Maly's  Jahresberichi  ttber  Thierchemie,  1892,  S.  9. 


552  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

Diamido-valeric  Acid,  or  Ornithin,  C4HT(  XH2)2COOH. — This  has  been  detected  by 
Jaffe  in  the  urine  and  excrements  of  fowls. 

«-£-Diamido-caproic  Acid,  or  Lysin,  CII2XII,CH2CH2CH2CHNH2- 
COOH. — This  is  a  hydrolytic  cleavage  product  of  proteid  after  boiling  with 
hydrochloric  acid,  or  baryta  water,1  and  may  be  similarly  obtained  from  gela- 
tin, from  vegetable  proteid  (eonglutin),  from  the  pancreatic  digestion  of 
proteid,  and  from  the  decomposition  of  the  protamine.     Other  bases  are: 

Histidin,  (  ,II(N\()„ a  base  derived  from  all  proteids  and  from  protamins. 

/NH2 
Arginin,2  CNHC 

\\H  —  CH2  —  CH2  —  CH2  —  CHNH2COOH,   is   also 
derived  from  all  proteids  and  from  protamins. 

PURIN  OR  ALLOXURIC  BODIES  AND   BASES. 

The  alloxnric  bodies  comprise  those  containing  in  combination  two  radicals, 
one  of  alloxan,  OC  <  xtu f  v \  >  CO,  the  other  of  urea.  The  skeletal  struc- 
ture of  all  alloxuric  bodies  may  be  written  thus : 


N— C 

/         1 

c       c 

— Nx 

\    1 

-K> 

N— C 

Alloxan. 

Urea. 

These  bodies  fall  into  three  groups,  that  of  hypoxanthin,  of  xanthin,  and  of 
uric  acid.  Bodies  belonging  to  the  first  two  groups  are  called  alloxuric  bases, 
or  more  commonly  xanthin  bases,  or  nuclei n  bases,  because  they  are  derived 
from  nucleiu.  The  strong  family  analogy  of  the  three  groups  is  shown  by 
the  following  reactions — results  of  heating  with  hydrochloric  acid  in  sealed 
tubes  at  180°  to  200°  :3 

C5H4N40  +  7H20  =  3NH3  +  C2H5M)2  +  C02  +  20H2O2. 

Hypoxanthin.  Glycocoll.  Formic  acid. 

05H4N4O2  +  6H20  =  3NH3  +  C2H6N02  +  2C02  +  CH202. 

Xanthin. 

C5H4N403  +  5H20  =  3NH3  +  C2H5N02  +  3C02. 

Uric  acid. 

Reference  to  the  formulae  below  will  show  that  the  molecules  of  C02  given 
off  correspond  t<»  the  number  of  CO  radicals  in  the  alloxuric  body,  while  the 
molecules  of  formic  acid  correspond  to  the  number  of  CH  groups. 

Emil  Fisher4  has  discovered  a   body  called  purin,  and  has  given  another 
classification.     The  chemical  series  of  the  purin  bodies  may  thus  be  presented  : 

1  Drechsel:  Archiv  far  Physiologie,  1891,  S.  248. 

•  Formula  by  Schulze  and  Winterstein :  Zeitechrift  far  physiologische  Chemie,  1899,  Bd.  26, 
S.  12. 

sKriiger:  Ibid.,  1894,  Bd.,  18,  S.  463. 

*  Berichte  der  deuUchen  ehetnisrlicn  <;,.« //,«■/, aft,  1899,  Bd.  32,  S.  435. 


THE  CHEMISTRY  OF  THE  ANIMAL   BODY.  553 

C5H4N403  C5H4N402  05H4N4O  C5H4N4. 

Uric  acid.  Xanthin.  Hypoxanthin.  Purin. 

To  purin  is  given  the  following  formula  : 

N  =  C  — H  IN  — 6C 


H  —  C       C-XH  20       50  —  N7 


\ 


\ 
N— C—  N  ''  3N  — 40- 

Purin.  Purin  nucleus 


//Q- 


For  the  convenience  of  chemical  description  the  atoms  of  the  purin 
nucleus  are  numbered  as  above,  since  the  chemical  constitution  varies  with 
the  locality  to  which  the  atoms  are  attached  to  the  nucleus.  The  purin  deriv- 
atives number  many  hundreds,  but  only  about  a  dozen  are  known  at  present 
to  have  physiological  significance. 

Hypoxanthin  is  6-oxypurin,  xanthin  is  2,  6-dioxypurin,  uric  acid  is 
2,  6,  8-trioxypurin,  adenin  is  6-amino-purin,  while  guanin  is  2-amino- 
6-oxypurin. 

Hypoxanthin,  xanthin,  adenin,  and  guanin  are  decomposition  products  of 
the  nucleins,  and  from  their  oxidation  uric  acid  is  derived. 

(a)   Purins. 

Purin,  C5H4N4.  This,  according  to  Emil  Fisher,  is  a  substance  which 
may  occur  in  the  body,  but  which  on  account  of  its  ready  decomposition  has 
not  yet  been  discovered  there. 

(6)  Monoxypurins. 

NH  — C  =  0 

I  I 

Hypoxanthin,  or  Sarcin,  H  —  C  C  —  NH\ 

||  ||  C  —  H.— This  is  found 

N   —  C—  N 

in  small  amount  in  the  tissues  and  fluids  of  the  body  and  in  the  urine. 
Hypoxanthin  is  derived  from  some  nucleins,  especially  those  contained  in 
the  sperm  of  salmon  and  carp,  through  the  action  of  water  or  dilute  acids. 

(c)  DlOXYPURINS. 

NH  — 0  =  0 

I  I 

Xanthin,  O  =  C  C  —  NH  \ 

C  —  H. — This  substance,  like  hvpoxan- 

NH  — C—  N 

thin,  is  found  in  the  tissues  and  fluids  of  the  body  and  in  the  urine.  It  is  a 
decomposition  product  of  some  nucleins  and  may  be  found  in  those  of  the 
pancreas,  thymus,  testicle,  carp  sperm,  dr. 

Methyl  Dioxypurins—  The  alkaloids  theophyllin,  theobromin,  and  caffein  occur  in 
tea,  coffee,  cocoa,  etc.,  and  are  habitually  taken  in  the  food.     Theophyllin  ( 1.  3-dimethyl- 


554  AN   AMERICAN   TEXT-BOOK   OF  PHYSIOLOGY. 

xanthin)  probably  loses  its  labile  3-methyl  in  the  body,  and  occurs  in  the  urine  as  1-methyl- 
xanthin.  In  like  manner  theobromin  (3,  7-dimethylxanthin)  is  converted  into  heteroxan- 
thin  (7-methylxanthin).  Caffein  (I.  3,  7-trimethylxanthin)  also  parts  with  its  3-metbyl- 
radicle  and  appears  in  the  urine  as  paraxanthin  (1,  7-dimethylxanthin).  Kriiger  and 
Salomon1  find  22. ::  errams  of  heteroxanthin,  31.3  grams  of  l-methylxanthin,  and  15.3  grams 
of  para-xanthin  in  L0,000  liters  of  urine,  or  much  more  in  quantity  than  the  true  nuclein 
bases  (xanthin.  etc.). 

That  theophyllin,  theobromin,  and  caffein  may  be  demethylated  in  the  tissue  is  an 
interesting  commentary  on  the  methylation  of  tellurium,  selenium,  and  pyridin  by  the 
tissues. 

(d)   MONOAMINOPURINS. 

N  =  C  — XH, 

I  I 
Adenin,  or  6-Aminopurin,  H  —  C       C  —  NH\ 

II  II  C-H. 
X  — C  —  X 

Adenin  is  found  in  the  blood,  the  tissues,  and  the  urine.  It  is  especially  a 
decomposition  product  of  thymus  nuclein,  although  other  nucleins  may  con- 
tain it.     Nitrous  oxide  converts  it  into  hypoxanthin. 

(e)  Amlnoxyptjrins. 

NH-  C=0 

I  I 
Guanin,  or  2-Amino-6-Oxypurin,  H2N  —  C          C  —  NH\ 

II  II  C-H 
N         C—  N  S 

This  also  is  found  as  a  decomposition  product  of  some  nucleins,  especially 
that  of  the  pancreas.  Combined  with  calcium  it  gives  the  brilliant  irides- 
cence to  fish-scales.2  It  is  found  in  the  fresher  layers  of  guano,  and,  accord- 
ing to  Voit,  is  here  very  probably  derived  from  the  fish  eaten  by  the  water- 
fowl. • 

Epiguanin,  or  7-Methyl-g-uanin. — This  has  been  found  in  the  urine,  and  like  the 
other  methylated  purins  may  very  likely  Vie  derived  from  the  fund  fed.3 

Episarcin  is  a  purin  hase  which  has  been  found  in  the  urine,  but  whose  configura- 
tion has  nol  yel  been  made  out. 

Carnin  is  said  to  occur  in  the  urine.     Its  composition  is  unknown. 

(/)  Trioxypurins. 

NH— C  -  O 

/  I 

Uric  Acid,  O  =  C  C— XH 

>CO. — This  acid  is  found  in  the  nor- 
MI_(  _xh 

mal   urine  in  small  amounts,  and  may  be  detected   in  the  blood  and  tissues, 

1  Zeitschriftfiir  physidogische  Chemie,  1898,  Bd.  26,  S.  350. 

2  Voil  :  Zeilschrifi  fur  wtssensehaftliche  Zodlogie,  Bd.  15,  S.  515. 

'  Kriiger  and  Salomon:  Zeitschriftfiir  physiologische  Chemie,  1898,  Bd.  26,  S.  389. 


THE    CHEMISTRY    OE    THE   ANIMAL    BODY.  555 

especially  in  gout.     It  is  the  principal  excrement  of  birds  and  snakes,  that  of 
the  latter  being  almost  pure  ammonium  urate. 

Preparation. — (1)  By  heating  glycocoll  with  urea  at  200°  : 

C2H5N02  +  3CO(NH2)2  ==  C5H4N403  +  3NH3  +  2H20. 

(2)  By  heating  the  amide  of  trichlorlactic  acid  with  urea : 

CCl3CHOH.CO.NH2  +  2CO(NH2)2  -  C5H4X4C)3  +  3HC1  +  NH3  +  H20. 

Properties. — Uric  acid  may  be  deposited  in  white  hard  crystals,  which  are 
tasteless,  odorless,  and  almost  insoluble  in  water,  alcohol,  or  ether.  (For  its 
solution  in  the  urine  see  p.  522.)  Preseuce  of  urea  adds  to  its  solubility.1  Its 
most  soluble  salts  are  those  of  lithium  and  piperazin.  Uric  acid  is  dibasic — 
that  is,  two  of  its  hydrogen  atoms  may  be  replaced  by  monad  elements. 

(1)  Nitric  acid  in  the  cold  converts  uric  acid  into  urea  and  alloxan: 

C5H4N403  +  0  +  H20  =  OC<^gZco>co  +  OC(NH2)2. 

Alloxan. 

(2)  Whereas,  if  the  hot  acid  acts,  it  produces  parabanic  acid: 

/NH  — CO\  /NH  —  CO 

OC<  >CO  +  0  =  OC<  j    +co2. 

\nh-cck  \NH-eo 

Parabanic  acid. 

(3)  Through  water  addition  parabanic  acid  becomes  oxaluric  acid: 

/NH  — C  =  0  /NH2 

OC<  I         +  H,0  =  OC< 

\NH-C  =  0  \NH.CO.COOH 

Oxaluric  acid. 

(4)  And  still  another  molecule  of  water  added  produces  oxalic  acid  and  urea: ' 

/NH2  COOH 

OC<  +H20=|  +OC(NH2)2. 

Nmco.cooH  cooH 

Oxalic  acid. 

The  above  reactions  lead  up  to  the  constitutional  formula  of  uric  acid,  and  show  its 
decomposition  into  urea  and  oxalic  acid  through  oxidation  ami  hydrolysis.  It  is  known 
that  uric  acid  when  fed  increases  the  amount  of  urea  in  the  urine,  and  it  is  possible  that 
the  oxalic  acid  in  the  urine  may  have  the  same  source. 

Uric  acid  oxidized  with  permanganate  of  potassium  is  converted  into  <il/<u<f<>ht, 

/NH— CH— NH\ 

OC<  |  >co. 

V\ll,    co-Nil/ 

a  substance  which  is  found  in  the  allantoic  fluid,  ami  in  the  urine  ofpregnanl  women  ami 
of  newborn  children,  and  in  the  urine  of  dogs  alter  feeding  thymus  (see  below). 

If  uric  acid  be  carefully  evaporated  with  nitric  acid  on  a  small  white  porcelain  cover, 
a  reddish  residue  remains,  which  moistened  with  ammonia  gives  a  brilliant  purple  color, 
due  to  the  formation  of  murexid,  C8H4(NH4)N608;  subsequent  addition  of  alkali  gives 
a  red  coloration.     This  is  known  as  the  murexid  test  and  is  very  delicate, 

The  Purin  Bases  in  the  Body. — All  true  nucleins  yield  one  or  more  of 

the  purin  bases.     Nucleins  are  combinations  of   nucleic  acid  and   proteid, 

'  G.  Riidel :  Archiv  fur  exper.  Pathologic  un<l  Ph<tmuik<>l<»jie,  1S93,  lid.  30,  S.  469. 
3  See  Bunge:  Physiologische  Chemie,  L894,  S.  312. 


556  AN  AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

except  the  nuclein  from  spermatozoa  in  which  the  acid  combines  with  pro- 
tamin.  The  simplest  indication  of  the  cleavage  of  nuclein  (see  Nuclein)  on 
chemical  treatment,  may  be  written  as  follows: 

Nuclein. 


Proteid.  Nucleic  acid. 


Phosphoric  acid.  Adenin. 

Guanin. 


Xanthin. 

Hypoxanthin. 

The  idea  that  the  purin  bodies  occurring  in  the  urine  of  mammals  are 
the  metabolic  products  of  nuoleins,  the  uric  acid  being  derived  from  the 
oxidation  of  the  bases,  was  made  especially  clear  by  the  experiments  of 
Horbaczewski.1  His  statement  that  feeding  nucleins  increases  the  purin 
bases  and  the  uric  acid  in  the  urine  has  been  frequently  confirmed.  He  also 
showed  that  if  fresh  spleen  pulp,  which  contains  no  purin  bodies,  be  per- 
mitted to  putrefy,  the  extract  will  contain  xanthin  and  hypoxanthin,  whereas 
if  the  spleen  pulp  be  shaken  with  the  air  uric  acid  is  produced,  being  oxi- 
dized from  these  bases.  Spitzer2  finds,  if  air  be  passed  through  spleen  and 
liver  extracts  digested  at  40°  with  the  exclusion  of  putrefaction,  that  uric 
acid  is  produced.  The  nuclein  bases  formed  decrease  with  the  increase  of 
uric  acid.  Hypoxanthin  and  xanthin  added  to  such  digests  are  readily  oxi- 
dized to  uric  acid,  as  are  adenin  and  guanin,  although  with  greater  difficulty. 
Extracts  of  the  kidney,  pancreas,  thymus,  and  blood  have  no  such  power. 
Feeding  uric  acid  and  nuclein  bases  increases  the  amount  of  urea  in  the 
urine.  Minkowski3  has  proved  that  after  feediug  hypoxanthin  uric  acid 
increases  in  the  urine,  showing  its  oxidation.  Minkowski  also  showed  after 
feeding  a  man  with  thymus,  the  nuclein  of  which  yields  principally  adenin 
with  some  guanin,  that  the  amount  of  uric  acid  was  increased  in  the  urine; 
the  same  food  fed  to  a  dog  increased  the  uric  acid,  and  allantoin,  an  oxidation 
product  of  uric  acid,  also  appeared.  Feeding  adenin  to  a  dog  did  not  in- 
crease the  uric  acid  or  allantoin  excretion,  but  on  autopsy  of  the  dog  there 
was  found  a  deposit  of  uric  acid  in  the  uriniferous  tubules  with  indications 
of  inflammatory  processes.  This  is  the  first  known  artificial  production  of  a 
deposition  of  uric  acid.  It  would  seem  that  the  adenin  in  combination  with 
nucleic  acid  in  thymus  may  be  readily  burned  to  uric  acid  in  such  a  way 
that  it  is  readily  excreted,  whereas  adenin  itself  behaves  differently.  Loewi4 
finds  that  the  same  amount  of  nuclei]]  food  fed  to  different  people  results  in 
tin  <ame  excretion  of  uric  acid.  He  therefore  concludes  that  all  the  purin 
bodies  liberated  in  metabolism  are  quantitatively  eliminated.    The  analysis  of 

1  Sitzungsberichte  der  Wiener  Akademie  der  Wissenschaft,  1891,  Bd.  100,  Abth.  iii.  S.  13. 

2  Pjliiffer's  Archiv,  1899,  Bd.  76,  S.  192. 

3  Archiv  fur  acper.  Patholorjir  umd  I'lmrmakologie,  1898,  Bd.  41,  S.  375. 

4  Ibid.,  1900,Bd.  44,  S.  1. 


THE   CHEMIST/,'  Y   OF   THE  ANIMAL   BODY.  557 

10,000  liters  of  urine1  has  shown  the  presence  of  10.11  grams  of  xanthin, 
8.5  grams  of  hypoxanthin,  and  3.54  grams  of  adenin. 

Xanthin  fed  to  birds  is  converted  into  uric  acid.  In  birds  the  formation  of  uric  acid 
depends  on  a  synthetic  union  of  ammonia  and  lactic  acid  in  the  liver,  since  on  extirpation 
of  the  liver  the  last  two  substances  appear  in  the  urine  in  amounts  proportional  to  the 
normally  formed  uric  acid  (see  p.  546). 

The  literature  on  the  subject  of  gout  is  enormous.  It  is  sufficient  to  re- 
mark here  that  it  is  not  even  known  whether  gout  is  due  to  an  increased  for- 
mation or  an  increased  retention  of  uric  acid.  The  amount  of  uric  acid  in  the 
blood  is  certainly  increased.  The  normal  amount  of  uric  acid  in  the  daily 
urine  is  put  at  0.7  gram,  that  of  the  purin  bases  at  0.1 325,2  although  this 
latter  may  be  too  high  on  account  of  the  presence  of  the  bases  derived  from 
tea  and  coffee.  The  amount  of  the  bases  may  be  quadrupled  in  leucocy- 
thsemia.3 

Diatomic  Dibasic  Acids,  CnH2n_204. 

COOH 

Oxalic  Acid,  |  . — This  is  found  as  calcium  oxalate  in  the  urine,  and 

COOH 
is  present  in  most  plants.     It  is   a  product  of  boiling  proteid   with  barium 
hydrate.     It  may  be  obtained  synthetically  by  heating  sodium  formate  : 

COONa 
2HCOONa=|  +2H. 

COONa 

Oxalic  acid  and  its  alkaline  salts  are  very  soluble  in  water.  Its  calcium  salts 
are  insoluble  in  water  and  dilute  acetic  acid,  but  are  soluble  in  the  acid  phos- 
phates of  the  urine. 

According  to  Lommel,4  oxalic  acid  is  a  product  of  metabolism,  and  is 
not  produced  proportionally  to  proteid  destroyed,  but  occurs  in  increased 
amounts  in  the  urine  when  nucleins  (thymus)  and  gelatin  arc  fed.  The 
occurrence  of  oxalic  acid  in  the  urine  after  feeding  nucleins  is  significant 
in  virtue  of  its  possible  origin  from  uric  acid  (see  Uric  Acid,  p.  55  I ).  Stones 
in  the  bladder  are  sometimes  composed  of  calcium  oxalate,  as  are  also  urinary 
sediments  when  formed  in  consequence  of  ammoniacal  fermentation. 

Succinic  Acid,  HOOC.C2H4.COOH—  This  has  been  detected  in  the 
spleen,  thymus,  thyroid,  in  echinococcus  fluid,  and  often  in  hydrocele  fluid.  It 
is  a  product  of  alcoholic  fermentation,  and  of  proteid  putrefaction.  It  is  often 
found  in  plants. 

Amido-succinic  Acid,  or  Aspartic  Acid,  HOOC.C2H3NH,.CXX)I  I . 
This  is  a  product  of  boiling  proteid  with  acid  or  alkalies,  and  it  is  also  formed 
under  the  influence  of  trypsin  in  proteid  digestion. 

1  Kruger  and  Salomon:  Zeitschrift fur physiologische  Chemie,  L898,  Bd.  26,  B.  850. 

2  Kriigerand  Wulff:  Ibid.,  1895,  Bd.  20,  S.  184.         3  Boudzynslri  and  <  tottlieb,  <>r-  at.,  8.  132. 
4  Deutsches  ArcMvfur  klinische  Medizin,  1899,  Bd.  til'.,  S.  599. 


558  AJV    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

Monamide  of  Amido-succinic  Acid,   or  Asparagin,   IT,NOC.C,H3NH.2.COOH 
— This  is  found  widely  distributed  in  plants,  especially  in  the  germinating  seed.     If  a  plant 
be  placed  in  the  dark  its  proteid  nitrogen  decreases,  whereas  the  non-proteid  nitrogen 
increases,1  the  cause  of  this  being  attributed  to  proteid  metabolism  with  the  production  of 

amido-  acids,  i.  < .  aspartic  and  glutamic  acids,  leucin,  and  tyrosin.  In  the  sunlight,  it 
is  believed,  these  bodies  arc  later  reconverted  into  proteid.  One  view  regarding  the  for- 
mation of  asparagin  is  based  theoretically  on  the  production  of  succinic  acid  from  carbo- 
hydrates (as  in  alcoholic  fermentation)  and  the  subsequent  formation  of  oxysucrinic  acid 
(or  malic  acid,  HOOC.C,H3OH.COOH),  which  the  inorganic  nitrogenous  salts  change 
to  asparagin.2  At  any  rate  asparagin  in  the  plant  has  the  power  of  being  constructed  into 
proteid.  Since  proteid  in  the  animal  body  may  yield  60  per  cent,  of  dextrose  in  its 
decomposition,  as  will  be  shown,  it  seems  fair  to  surmise  that  the  synthesis  of  proteid  in 
the  plant  may  in  part  depend  upon  the  union  of  asparagin  or  similar  amido-  compounds 
wit  li  the  carbohydrates  present.  Asparagin  if  fed  is  converted  into  urea.  It  forms  no 
proteid  synthesis  in  tin'  animal,  and  lias  only  a  very  small  effect  as  a  food-stuff.3 

Glutamic  acid,  H00C.(,I1NI1,.(,II,.*CH2.C001I.— This  is  found  as  a  cleavage- 
product  of  tryptic  digestion  in  the  intestinal  canal.  Glutamin,  its  amido- compound,  is,  like 
asparagin,  widely  distributed  in  the  vegetable  kingdom  and  in  considerable  amounts.  It 
probably  plays  the  same  role  as  asparagin  in  the  plant.  Glutamin  is  more  soluble  than 
asparagin  and  is  therefore  less  easily  detected. 

Compounds  of  Triatomic  Alcohol  Radicals. 

Glycerin,  or  Propenyl  Alcohol,  CH2OH.CHOH.CH2OH.  The  glycerin 
esters  of  the  fatty  acids  form  the  basis  of  all  animal  and  vegetable  fats. 
Glycerin  is  furthermore  formed  in  small  quantities  in  alcoholic  fermentation. 

Preparation. — (1)  Through  the  action  of  an  alkali  on  a  fat,  glycerin  and  a 
soap  are  formed,  a  process  called  saponification: 

2C3H5(C18H3502)3  +  6XaOH  =  2C3H5(OH)3  +  GNaC^O,. 

Stearin.  Sodium  stearate. 

(2)  Fats  may  be  decomposed  into  glycerin  and  fatty  acid  by  superheated 
Steam,  and  likewise  by  the  fat-splitting  ferment  in  the  pancreatic  juice.  Thus, 
if  a  thoroughly  washed  butter-ball,  consisting  of  pure  neutral  fat,  be  colored 
with  blue  litmus,  and  a  drop  of  pancreatic  juice  be  placed  upon  it,  the  mass 
will  gradually  grow  red  in  virtue  of  the  fatty  acid  liberated  from  its  glycerin 
combination.     This  reaction  takes  place  in  the  intestine. 

If  fatty  acid  la-  led,  the  chyle  in  the  thoracic  duet  is  found  to  contain  much 
neutral  fat.'  This  synthesis  indicates  the  presence  of  glycerin  in  the  body — 
perhaps,  in  this  case,  in  the  villus  of  the  intestine:  the  source  of  this  glycerin, 
whether  from  proteid  or  carbohydrates,  is  problematical.  If  glycerin  be  1'ed, 
only  little  is  absorbed  (since  diarrhoea  ensues),  and  of  thai  little  some  appears 
in  the  urine.      It  seems, therefore,  to  be  oxidized  with  difficulty  in  the  body. 

Glycerin  Aldehyde,  IIOCH2.CHOH.CHO,  and  Dioxyacetone,  HOCH.2.CQ.CH2 
Oil. — These  substances  are  formed  by  the  careful  oxidation  of  glycerin  with  nitric  acid, 
and  together  are  termed  glycerose.     They  ha\e  a  sweet  taste  and  are  the  lowest  known 

1  Schulze  and  Kisser:   Landwirthschatfliche  Versucks-Staiion,  1889,  Bd.  36,  S.  1. 

'  Miiller:  Ibid.,  1886,  Bd.  33,  S.  326. 

3  See  Voit  :  Zeitschrift  fur  Biologic,  1892,  Bd.  29,  B.  126. 

*  Munk:   Virchovfs  Archiv,  1880,  Bd.  80,  S.  17. 


THE   CHEMISTRY    OF   THE  ANIMAL   BODY.  559 

members  of  the  glycose  (sugar)  series — i.  e.  substances  which  are  characterized  by  the 
presence  of  either  aldehyde-alcohol,  — CHOH — CHO,  or  ketone- alcohol,  — CO — CH.<  MI, 
radicals.  The  constituents  of  glycerose,  from  the  number  of  their  carbon  atoms,  are 
called  trioses.  On  boiling  glycerose  with  barium  hydrate  the  twu  constituents  readily 
unite  to  form  i- fructose  (levulose). 

Glycerin  Phosphoric  Acid,  (HO)2C3H5.H2P04.— This  is  the  only  ethe- 
real phosphoric  acid  in  the  urine.     It  is  luiind  in  mere  traces. 

Lecithin,    C3H/(C"H2U-A)2 

3    3\O.PO.(OH).O.C2H4.N(CH3)3OH.— Lecithin     is     found 

in  every  cell,  animal  or  vegetable,  and  especially  in  the  brain  and  nerves. 
It  is  found  in  egg-yolk,  in  muscles,  in  blood-corpuscles,  in  lymph,  pus-cells, 
in  bile,  and  in  milk.  On  boiling  lecithin  with  acids  or  alkalies,  or  through 
putrefaction  in  the  intestinal  canal,  it  breaks  up  into  its  constituents,  fatty 
acids,  glycerin  phosphoric  acid,  and  cholin  (see  p.  543),  substances  which  the 
intestine  may  absorb.  The  fatty  acids  may  be  stearic,  palmitic,  or  oleic,  two 
molecules  of  different  fatty  acids  sometimes  uniting  in  one  molecule  of 
lecithin  :  hence  there  are  varieties  of  lecithins.  Through  further  putrefaction 
cholin  breaks  up  into  carbonic  oxide,  methane,  and  ammonia.1  Lecithin 
treated  with  distilled  water  swells,  furnishing  the  reason  for  the  "  mvelin 
forms"  of  nervous  tissue.  Lecithin  is  readily  soluble  in  alcohol  and  ether. 
It  feels  waxy  to  the  touch.  Protagon,  which  has  been  obtained  especially 
from  the  brain,  is  a  crystalline  body  containing  lecithin  and  cerebri)} — which 
is  a  glucoside  (a  body  separable  into  proteid  and  a  sugar).  The  chemical 
identity  of  protagon  is  shown  in  that  ether  and  alcohol  will  not  extract  lecithin 
from  it.2  Protagon  readily  breaks  up  into  its  constituents.  While  protagon 
seems  to  be  regarded  as  the  principal  form  in  which  lecithin  occurs  in  the 
brain,  simple  lecithin  is  believed  to  be  present  in  the  nerves  and  other  organs. 
This  subject  has  not  been  properly  worked  out.  Noll1  states  that  the 
quantity  of  protagon  in  the  spinal  cord  may  amount  to  2o  per  cent,  of  the 
dry  solids,  in  the  brain  to  22  per  cent.,  and  in  the  sciatic  nerve  to  7.5  per 
cent.  Regarding  the  synthesis  of  lecithin  in  the  body,  or  the  physiological 
importance  of  the  substance,  absolutely  nothing  is  known. 

Fat  in  the  Body. — Animal  and  vegetable  fats  consisl  principally  of 
a  mixture  of  the  triglycerides  of  palmitic,  stearic,  and  oleic  acids.  In  the 
intestines  the  fat-splitting  ferments  convert  a  small  portion  offal  into  glycerin 
and  fatty  acid  ;  the  fatty  acid  unites  with  alkali  to  form  a  soap,  in  the  presence 
of  which  the  fat  breaks  up  into  fine  globules  called  an  emulsion  :  the  fat-split- 
ting ferment  then  acts  further  on  the  fat,  probably  converting  it  all  into  tatty 
acid  and  glycerin.'  A  line  emulsion  of  lanolin  ( fatty  acid  in  combination  with 
cholesterin,  isocholesterin,  etc.)  is  not  absorbed,  because  the  intestine  dues 
not  break  up  the  combination/  and  the  melted  particles  themselves  cannot 

1  JIasebroek:  Zeitschrift  fur  physiologische  Chemie,  1888,  Bd.  12,  8.  1  18. 

2  Gamgee  and  Blankenhorn:  Journal  of  Physiology,  1881,  vol.  ii.  p.  113. 

*  Zeitschrift  fur  physiologische  Chemie,  L899,  Bd.  27,  S.  370. 

*  Frank,  ( ).  :  Zeitschrift  fur  Biologic,  1898,  Bd.  36,  8.  :><>*. 
6  Counstein  :  Archiv  fur  Physiologie,  L899,  S.  30. 


560  AN   AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

be  absorbed.  When  the  fatty  acids  arc  produced  they  unite  with  the  alkali 
of  the  intestines  to  form  soaps.  The  solution  of  these  soaps  is  greatly  aided 
by  the  bile.1  The  tissue  of  the  villus  has  the  power  to  unite  synthetically  the 
absorbed  soap  and  glycerin  to  form  neutral  fat. 

It  should  be  remembered  that  the  changes  necessary  for  the  absorption  of 
fat  may  also  take  place  in  a  cleansed  isolated  loop  of  the  intestine.2 

Fat  may  likewise  be  derived  from  ingested  carbohydrates.  The  chemical 
derivation  of  fatty  acid  from  carbohydrates  has  already  been  mentioned  in 
the  case  of  formic,  acetic,  propionic  (see  p.  537),  and  butyric  acids.  The  fatty 
acids  of  fusel  oils  are  likewise  formed  from  carbohydrates  in  fermentation. 
The  laboratory  synthesis  of  sugar  from  glycerin  has  been  already  related. 
These  reactions,  however,  furnish  only  the  smallest  indication  of  the  large 
transformation  of  carbohydrates  into  fat  possible  in  the  body. 

If  geese  be  fed  with  rice  in  large  quantity,  and  the  excreta  and  air  respired  be  ana- 
lyzed, it  may  be  shown  that  carbon  is  retained  in  large  amount  by  the  body,  in  amount 
too  great  to  be  entirely  duo  to  the  formation  of  glycogen,  and  must  therefore  have  been 
deposited  in  the  form  of  fat.s  Such  fattening  of  geese  produces  the  delicate  pdti  de  foie 
gras.     The  principle  has  been  established  in  the  case  of  the  dog  as  well.4 

The  formation  of  fat  from  proteid  (fatty  degeneration)  is  believed  to 
take  place  in  some  pathological  cases  (see  p.  513).  Recollection  of  the  fact 
that  proteid  may  yield  60  percent,  of  sugar  aids  in  the  comprehension  of  this 
problem.8 

Other  usually  cited  proofs  of  the  formation  of  fat  from  proteid  include  the  conversion 
of  casein  into  fat  incident  to  the  ripening  of  cheese  ;  and  the  transformation  of  muscle  in 
a  damp  locality  into  a  cheesedike  mass  called  adipocere,  which  is  probably  effected  by 
bacteria.6  Adipocere  contains  double  the  original  quantity  of  fatty  acid,  occurring  as  cal- 
cium, and  sometimes  as  ammonium  salts. 

Experiments  of  C.  Voit  show  that  on  feeding  large  quantities  of  proteid.  not  all  the 
carbonic  acid  is  expired  that  belongs  to  the  proteid  destroyed  as  indicated  by  the  nitrogen 
in  the  urine  and  feces.  The  conclusion  follows  that  a  non-nitrogenous  substance  has  been 
stored  in  the  body.  Too  much  carbon  is  retained  to  be  present  only  in  the  form  of  glyco- 
gen ;  fat  from  proteid  must  therefore  have  been  stored.7  The  formation  of  fat  normally 
from  proteid  has  been  combated  by  Pfluger,  it  would  seem  without  proper  foundation. 
For  behavior  oi*  fat  in  the  cell  see  p.  558. 

Oleic  Acid,  C1SII3402. — This  acid  belongs  to  the  series  of  fatty  acids  hav- 
ing the  formula  CDH2n_202.  Its  glyceride  solidifies  only  as  low  as  +4°  C.  It  is 
the  principal  compound  of  liquid  oils.  Pure  stearin  is  solid  at  the  body's 
temperature,  but  mixed  with  olein  the  melting-point  of  the  mixture  is  reduced 
below  the  temperature  of  the  body  and  its  absorption  is  thereby  rendered  possi- 
ble.    The  fat  in  the  body  is  all  in  a  fluid  condition,  due  to  the  presence  of  olein. 

1  Moore  and  Rockwood :  Journal  of  Physiology,  1897,  vol.  xxi.   p.  58. 

I  lunningham  :   Ibid.,  1898,  vol.  23,  p.  209. 
5  Voit:  Abstract  in  Jahresberichi  fiber  Thierchemie,  1885,  lid.  15,  S.  51. 

4  Rubner:  ZeUackrifi  fur  Biologie,  1886,  Bd.  22,  S.  272. 

5  Kay,  McDermott  and  Lusk  :  American  Journal  of  Physiology,  1899,  vol.  3,  p.  139. 
'■  Bead  Lehmann:  Abstract  in  Jahresberirht  fiber  Thierchemie,  1889,  Bd.  19,  S.  51b. 

7  Erwin  Voit  :  Munchener  medicinische  Wochenschrift,  No.  26,  1892  ;  abstract  in  Jahresbericht 
iiber  Thierchemie,  1892,  S.  34 ;  Cremer,  M.  :   Zeitsehrift  fur  Biologic,  1899,  Bd.  38,  S.  309. 


THE    CHEMISTRY    OE    THE   ANIMAL    BODY.  561 

Carbohydrates. 

The  important  sugar  of  the  blood  and  the  tissues  is  dextrose.  It  is 
derived  from  the  hydration  of  starchy  foods,  and  from  proteid  metabolism. 
From  dextrose  the  lactic  glands  probably  manufacture  another  carbohydrate, 
milk-sugar.  Cane-sugar  forms  an  article  highly  prized  as  a  food.  Thestudy 
of  the  various  sugars  or  carbohydrates  is  of  especial  interest,  because  their 
chemical  nature  is  now  well  known. 

Carbohydrates  were  formerly  denned  as  bodies  which,  like  the  sugars  and 
substances  of  allied  constitution,  contain  carbon,  hydrogen,  and  oxygen,  the 
carbon  atoms  being  present  to  the  number  of  six  or  multiples  thereof,  the 
hydrogen  and  oxygen  being  present  in  a  proportion  to  form  water.  Glycoses 
include  the  monosaccharides  like  dextrose,  C6II1206 ;  disaccha rides  include, 
for  example,  cane-sugar,  C12H22Ou,  which  breaks  up  into  dextrose  and  levu- 
lose,  while  polysaccharides  comprise  such  bodies  as  starch  and  dextrins,  which 
have  the  formula  (C6H10O5)n. 

In  recent  years  the  term  glycose  has  been  extended  to  cover  bodies  having 
three  to  nine  carbon  atoms  and  possessing  either  the  constitutiou  of  an 
aldehyde-alcohol,  — CH(OH)CHO,  called  aldoses,  or  of  a  ketone-alcohol, 
— COCH2OH,  called  ketoses.  These  bodies  also  have  hydrogen  and  oxygen 
present  in  a  proportion  to  form  water,  and  the  number  of  carbon  atoms  always 
equals  in  number  those  of  oxygen.  According  to  their  number  of  carbon  atoms 
they  are  termed  trioses,  tetroses,  pentoses,  hexoses,  heptoses,  octoses.  and  non<  >-i  is. 

It  has  been  shown  (foot-note,  p.  545)  how  from  the  asymmetric  carbon  atom  in  lactic 
acid  two  configurations  are  derived.  If  a  body  (such  as  trioxybutyric  acid)  contains  two 
asymmetric  carbon  atoms,  four  configurations  are  possible, 

CH2OH                   CH2OH                 (I  I, OH  CILOH 

HCOH  OHCH  OHCH"  HCOH 

HIM  MI  OHCH                    HCOH  OHCH 

COOH                    COOH                 COOH  COOH 

Similarly  among  the  glycose-aldoses,  a  triose  has  two  modifications  ;  a  tetrose,  four ;  a  pen- 
tose, eight:  a  hexose,  sixteen,  etc.  Thus  in  the  following  formula  by  the  variations  of  H 
and  OH  on  the  four  asymmetric  carbon  atoms,  sixteen  possible  hexoses  may  be  obtained. 

CH2OH 

— C— 

— c— 
— c— 
-c— 

CHO 

The  carbohydrates  have  well-defined  optical  properties,  rotating  polarized  light  to  the 
right  or  left,  and  were  therefore  originally  designated  as  d-  (dextro-)  and  I-  (lsevo-)  respec- 
tively. An  inactive  (/-)  form  consists  in  an  equal  mixture  of  the  two  others;  at  present, 
however,  thed-  may  signify  a  chemical  relation  to  dextrose:  thus  levulose,  which  is  ordinary 
fruit  sugar  and  rotates  polarized  light  to  the  left,  is  called  d-  fructose,  on  account  ol  its  deriva- 
tion from  dextrose.  Where  the  Oil  group  is  attached  on  the  right  it  may  he  indicated  by 
the  sign +,  on  the  left  by — ,  or  the    |    (Ml  may  he  written  below,  th< — Oil  above. 

II       II    Oil    II 
orCH.,011   T       C      ('     C    (410 
(Ml   OH    II  (Ml 


Vol.  I. 


CH( ) 

CIIO 

iiroii 

c+ 

ouch 

c— 

1KMMI 

C+       ' 

HCOH 

C-f- 

CILOH 

CH2OH 

d-Glucose. 

562  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

The  Glycoses. 

The  triose  called  glycerose  has  already  been  described. 

A  tetrose  called  erythrose,  which  is  the  aldose  of  erythrite,  C4H6(OH)4,  a 
tetratomic  alcohol,  is  known. 

Of  the  possible  pentoses,  arabinose,  xylose,  and  rhamnose  (methyl-arabinose) 
occur  in  the  vegetable  kingdoms  in  considerable  quantity.  They  may  be 
absorbed  by  the  intestinal  canal.1  Pentoses  are  found  in  the  urine  in  rare 
cases.2  Some  nucleins,  especially  those  of  the  pancreas  and  thymus,  yield 
pentoses  on  decomposition.  Subcutaneous  injection  of  arabinosc,  xylose,  and 
rhamnose  results  in  their  excretion  to  the  extent  of  more  than  50  per  cent, 
in  the  urine.3     The  rest  may  be  burned. 

Hexoses,  or  Glucoses. — Through  the  oxidation  of  hexatomic  alcohols 
there  may  be  obtained,  first,  glucoses,  then  monocarbonic  acids,  and  lastly 
saccharic  acid,  or  its  isomer  mucic  acid  : 

C5H6(OH)5CH2OH.        C5H6(OH)5CHO.        C5H6(OH)5COOH. 

Mannite.  Mannose  Mannonic  acid, 

(and  levulose). 

C5H6(OH)4(COOH)2. 

Saccharic  acid. 

Mannose  and  levulose  are  respectively  the  aldose  and  ketose  of  mannite, 
galactose  is  the  aldose  of  duleite,  whereas  glucose  is  probably  the  aldose  of 
sorbite — duleite  and  sorbite  being,  like  mannite,  hexatomic  alcohols. 

Properties. — (1)  The  hexoses  are  converted  into  their  respective  alcohols  on 
reduction  with  sodium  amalgam. 

(2)  The  hexoses  act  as  reducing  agents,  converting  alkaline  solutions  of 
cuprous  oxide  salts  (obtained  through  presence  of  tartrate)  into  red  cuprous 
oxide,  which  precipitates  out  (Trommer's  test).  Levulic  acid  is  among  the 
products  formed  (see  p.  538).  Of  the  higher  saccharides  only  maltose  and 
milk-sugar  give  this  reaction. 

(3)  Strongly  characteristic  are  the  insoluble  crystalline  compounds  formed 
by  all  glycoses  with  phenvlhydrazin,  called  osazones  (see  p.  534) : 

06H12O6  +  2ILX.X  I  I(C6H5)  =  C6H10O4(:N.NH.C6H5)2  +  2H20  +  H2. 

Levulose.  Phenvlhydrazin.  Glycosazone. 

Levulose,  dextrose,  and   mannose  give  the  same  glycosazone.      The    glycos- 
azones  are  decomposed  into  osones  by  fuming  hydrochloric  acid  : 

C6H10O4(:N.NH.C6H6)2  +  2H20   ==  C6H10O6  +  2H2N.NH.C6H5. 

Glycosone. 
Osones    are    converted    into    sugar    by   nascent    hydrogen.       The    osone    de- 
rived from  levulose,  dextrose,  and  mannose  yields  levulose  by  this  treatment, 
and   the  transformation  of  dextrose  and  mannose  into   levulose  is  therefore 
demonstrated. 

1  Weiske:  Zeitschrift  fiir  physiologischi  Chemie,  1895,  Bd.  20,  S.  489. 
>  Salkowski  :  Zeitschrift  fiir  phy&iologische  Chemie,  1899,  lid.  27,  S.  507. 
3  Vi.it.  F.  :  Deutsche*  Archiv  fiir klinische  Medizin,  Bd.  58,  S.  523. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  563 

(4)  Only  trioses,  hexoses,  and  nonoses  are  capable  of  alcoholic  fermenta- 
tion. 

Synthesis  of  the  Glucoses. — Formose  (see  p.  533)  may  be  purified  by  means  of 
phenylhydrazin  as  above,  so  that  pure  /-fructose  is  obtained  ;  this  treated  with 
sodium  amalgam  yields  /-mannite,  which  on  oxidation  is  converted  into  /-man- 
nonicaeid  ;  this  last  is  separated  by  a  strychnin  salt  into  its  two  components  ■ 
the  rf-mannonic  acid  is  divided  and  one  part  treated  with  hydrogen,  with  result- 
ing d-mannose,  which,  as  has  been  shown  above,  is  convertible  into  (/-fructose 
or  ordinary  fruit-sugar ;  the  second  part  of  the  c/-mannonic  acid  treated  with 
chinolin  is  transformed  through  change  in  configuration  into  its  isomer, 
(/-gluconic  acid,  which  on  reduction  yields  (/-glucose,  or  ordinary  dextrose. 
This  shows  the  preparation  of  the  common  sugars  from  their  elements.  The 
transformation  of  levulose  into  dextrose  is  especially  to  be  noted,  since  it  takes 
place  in  the  body. 

K    H     OHH 

(/-Glucose,  Dextrose,   Grape-sugar,  CH2OH  C      C      C      C     CHO.— 

OH  OH  H  OH 
This  is  the  sugar  of  the  body.  It  is  found  in  the  blood  and  other  fluids  and  in 
the  tissues  to  the  extent  of  0.1  per  cent,  and  more,  even  during  starvation.  The 
principal  source  of  the  dextrose  of  the  blood  is  that  derived  from  the  digestion 
of  starch,  and  also  of  cane-sugar,  in  the  intestinal  tract.  Dextrose  is  likewise  pro- 
duced from  proteid,  for  a  diabetic  patient  fed  solely  on  proteid  may  still  excrete 
sugar  in  the  urine.  Minkowski1  finds  that  in  starving  dogs  after  extirpation 
of  the  pancreas  the  proportion  of  sugar  to  nitrogen  is  2.8  : 1.  The  same  ratio 
has  been  shown  to  exist  in  phlorhizin  diabetes  in  fasting  rabbits2  and  goats3 
when  the  drug  is  frequently  administered.  After  frequent  dosage  of  phlorhizin 
to  fasting,  meat-fed,  or  gelatin-fed  dogs,  the  ratio  dextrose  :  nitrogen  approxi- 
mates 3.75  : 1.  Since  1  gram  of  N  in  the  urine  corresponds  (neglecting  the  faecal 
N)  to  6.25  grams  of  proteid  destroyed,  therefore,  3.75  grams  ot  sugar  must 
have  arisen  from  <>.25  grams  of  proteid  (including  gelatin).  In  other  words, 
there  has  been  a  production  from  the  proteid  molecule  of  60  per  cent. 
of  dextrose,  which  contains  nearly  60  per  cent,  of  the  physiologically  avail- 
able energy  of  the  proteid  consumed.4  A  similar  large  excretion  of  dextrose 
has  been  noted  in  cases  of  human  diabetes  mellitus.* 

In  pancreas  diabetes  the  pancreas  may  perhaps  manufacture  a  ferment 
which,  supplied  from  the  lymph  of  the  pancreas''  to  the  tissues,  becomes  the 
first  cause  of  the  decomposition  of  dextrose,  and  in  whose  absence  diabetes 
ensues.  Excess  of  dextrose  in  the  body  is  stored  up,  especially  in  the  liver- 
cells,  as  glycogen,  which  is  the  anhydride  of  dextrose )  the  glycogen  may  be 
afterwards  reconverted  into  dextrose.  The  presence  of  sugar  in  the  body  in 
starvation,  even  when  little  urea  may  be  detected  there,  shows  the  readier  excre- 

1  Arehivfiir  Exper.  Paihologie  wnd  Pharmakologie,  L893,  Bd.  31,  8.  85. 

a  Lusk  :  Zeitachriftfiir  Biologic,  1898,  Bd.  36,  S.  82.  i  busk:  Unpublished. 

*  Reilly,  Nolan,  and  Lusk:   American  Journal  of  Physiology,  1898,  vol.  i.  j>.  895. 

s  Kmnpf:   Berliner  Minischer  Wbchenschrift,  1898,  Bd.  24,  Heft  43. 

■  Biedl  :  Centralbatt  fur  Physiologic,  1898,  Bd.  12,8.624. 


564  AN   AMERICAN    TEXT-BOOK   OF  PHYSIOLOGY. 

tioii  of  the  nitrogenous  radical  of  proteid.     Traces  of  dextrose  are  found  in 
normal  urine. 

1  >"\trose  is  a  sweet-tasting-  crystalline  substance;  its  solutions  rotate  polar- 
ized light  to  the  right. 

Jecorin,  a  substance  found  in  the  liver  and  the  blood,  yields  dextrose  on 
decomposition.     It  is  said  to  be  a  glycose-lecithin.1 

Glucosainin,  C6Ifu<  >.X  !!._,. —  This  is  yielded  as  a  decomposition  product 
of  some  proteids.  Egg  albumin,  for  example,  yields  8  percent,  of  gluco- 
sainin.     It  reduces  copper  solutions,  and  has  been  mistaken  for  dextrose. 

H    H    OH 

rZ-Fructose,  Levulose,  Fruit-sugar,  CH2OH  C      C      C     COCH2OH. — 

OHOHH 
This  occurs  in  many  fruits  and  in  honey.  It  is  sweeter  than  dextrose,  and 
rotates  polarized  light  to  the  left.  It  is  a  product  of  the  decomposition  of 
cane-sugar  in  the  intestinal  canal.  If  levulose  be  fed.  any  excess  in  the  blood 
may  be  converted  into  glycogen,  and  through  the  glycogen  into  dextrose.  It 
is  possible  thus  to  convert  50  per  cent,  of  the  levulose  fed  into  dextrose.2 
When  levulose  is  fed  to  a  diabetic  patient,  it  may  be  burned,  though  power  to 
burn  dextrose  has  been  lost.3 

H    OHOHH 

d-  Galactose,  CH2OH  C  C  C  C  CHO.— This  is  found  combined 
OIIH  H  OH 
with  proteid  in  the  brain,  forming  the  glucoside  cerebrin.  It  is  produced 
together  with  dextrose  in  the  hydrolytic  decomposition  of  milk-sugar.  It  does 
not  undergo  alcoholic  fermentation,  at  least  not  with  Saccharomyces  apiculatus. 
When  fed  it  may  in  part  be  directly  burned  or  in  part  converted  into 
glycogen. 

The  Disaccharides,  C12H22On. 

These  are  di-multiple  sugars  in  ether-like  combination.  To  cane-sugar  and 
milk-sugar,  Fisher  has  ascribed  the  following  formulae  : 4 

Cane-sugar.  M  ilk-sugar. 

.CH- — -__n    CH2OH 
n/CHOH      U\C 
u\CIIOH  CHOH 

CH  O    CHOH 

CHOH  (II 

CHjOH  CH2OH 

Dextrose  group.        Levulose  group. 

Cane-sugar,  or  Saccharose. — Cane-sugar,  obtained  from  the  sugar-cane 
and  the  beet-root,  is  largely  used  to  flavor  the  food,  and  likewise  assumes 
importance  as  a  food-stuff.  On  boiling  with  dilute  acids,  cane-sugar  is  con- 
verted through  hydrolysis  into  a  mixture  of  levulose  and  dextrose.     The  same 

1  Bing  :   Omtralblatt  fur  Physiologie,  1898,  Bd.  12,  S.  209. 

7  Minkowski :  Archie  fur  Pathologic  und  PharmaJeologie,  L893,  Bd.  31,  S.  157. 

3  Loc.  cit.  *  Berichte  der  deutschen  chemischen  Gesellschaft,  1894,  Bd.  26,  S.  2400. 


CH,OH 

CHOH 

CH 
n/CHOH 
u\CHOH 

CH       — O- 

CHO 
CHOH 
CHOH 
CHOH 
CHOH 
-CH2 

Galactose  group. 

Dextrose  group, 

THE   CHEMISTRY   OF   THE  ANIMAL   BODY.  565 

result  is  obtained  by  warming  with  0.05  to  0.2  per  cent,  hydrochloric  acid  at 
the  temperature  of  the  body.1  This  inversion,  therefore,  takes  place  in  the 
stomach.  In  the  intestinal  canal  the  inversion  is  accomplished  through  the 
action  of  a  ferment  present  in  the  intestinal  juice.  Subcutaneous  injection 
of  cane-sugar  results  in  its  quantitative  excretion  through  the  urine  j 2  but 
fed  per  os,  cane-sugar  is  converted  into  dextrose  and  levulose,  which  may  be 
burned  in  the  body. 

Milk-sugar,  or  Lactose. — This  is  found  in  the  milk  and  in  the  amniotic 
fluid.  It  is  probably  manufactured  from  dextrose  in  the  mammary  glands, 
for  the  blood  does  not  contain  it.  It  is  always  present  in  the  urine  during 
the  first  days  of  lactation,  but  is  not  found  there  antepartum.3  It  readily 
undergoes  lactic  fermentation,  producing  lactic  acid,  which  then  causes  clotting 
of  the  milk.  This  fermentation  may  take  place  in  the  intestinal  tract.  Boiling 
with  dilute  apids  splits  up  milk-sugar  into  galactose  and  dextrose.  This  decom- 
position probably  does  not  take  place  in  the  stomach.  The  intestinal  juice 
causes  this  transformation,  especially  in  suckling  animals,4  and  lactase  of  the 
pancreatic  juice  will  also  split  milk-sugar.5  Milk-sugar  injected  subcutane- 
ously  in  man  is  quantitatively  eliminated  through  the  kidney.6  It  must, 
therefore,  undergo  inversion  in  the  intestine  into  galactose  and  dextrose 
before  it  can  be  burned. 

Isomaltose. — This  is  the  only  disaccharide  which  has  been  synthetically 
obtained,  having  been  produced  by  boiling  dextrose  with  hydrochloric  acid. 
It  ferments  with  difficulty  and  forms  an  osazone  which  melts  at  150°-15o°. 
It,  with  dextrin,  is  a  product  of  the  action  of  diastase  and  of  the  diastatic 
enzymes  found  in  saliva,  pancreatic  juice,  intestinal  juice,  and  blood  upon 
starch  and  glycogen.  Through  further  action  of  the  same  ferments  isomaltose 
is  converted  into  maltose. 

Maltose. — Maltose  (and  dextrin)  are  the  end-products  of  the  action  of 
diastase  on  starch  and  glycogen,  the  process  being  one  of  hydrolysis : 

3C6Hl0O5  +  H20  =  Ci2H22Ou  +  C6HJ0O5. 

Maltose.  Dextrin. 

It  is  likewise  a  product  of  the  diastatic  action  of  ptyalin  (saliva),  amylopsin 
(pancreatic  juice),  and  of  ferments  in  the  intestinal  juice  and  in  the  blood. 
Maltose  readily  undergoes  alcoholic  fermentation  and  forms  an  osazone  which 
melts  at  206°.  It  is  converted  into  dextrose  by  boiling  with  acids.  Certain 
ferments  convert  maltose  (and  dextrin)  into  dextrose  (see  Starch). 

(Vj/lulose  Group,  (C6IT10Or,)n. 

Cellulose. — This  is  a  highly  polymerized  anhydride  of  dextrose,  perhaps  also  of  man- 
nose.     It  tonus  the  cell-wall  in  the  plant.     It  undergoes  putrefaction  in  the  intestinal 

1  Ferris  and  Lusk  :  American  Journal  <>j  Physiology,  L898,  vol.  1,  p.  "J77 
»  Voit,  F. :   Deutsehes  Archiv fur  klinische  Medizin,  1897,  !'.<!   58,  8.  523. 

3  Lemaire:   Zeitsckriftfur  p/u/siologische  Chemie,  1896,   Bd.  10,  S.  44"J. 

4  Weinland  :  ZeiUchrift  fur  Biologic,  1899,  Bd.  38,  S.  16. 

5  Ibid.,  1899,  Bd.  38,  S.  607.  "  \  oit,  F. :  hoc.  cit. 


566  AN  AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

canal,  especially  in  herbivore  (see  p.  532).  and  owing  to  the  production  of  fatty  acids  it  may 
have  value  as  a  food.  In  man  only  young  and  tender  cellulose  is  digested,  such  as  occurs 
in  lettuce  and  celery.  The  bulk  of  herbivorous  fecal  matter  consists  of  cellulose.  Cellulose 
is  only  with  difficulty  attacked  by  acids  and  alkalies.  Tunicin,  found  among  the  tunicates, 
is  identical  with  cellulose,  so  that  the  substance  is  not  solely  characteristic  of  the  vegetable 
kingdom. 

Starch,  (C6H10O5)20. — This  substance  on  boiling  with  dilute  acids  breaks 
down  by  hydrolysis  principally  to  dextrose.  It  is  found  in  plants,  and 
may  be  manufactured  by  them  from  cane-sugar,  dextrose,  levulose,  and  from 
other  sugars.  It  forms  a  reserve  food-stuff,  being  converted  into  sugar  as  the 
plant  requires  it — in  winter,  for  example.  Starch  gives  a  blue  color  with 
iodine.  According  to  recent  investigations1  starch  is  said  to  be  broken  up  by 
diastase  into  five  successive  hydrolytic  cleavage-products  as  follows :  (1)  Amylo- 
dextriu  ( ( 'jdlajO,^,  a  substance  giving  a  deep-blue  color  with  iodine.  This 
is  next  changed  to  (2)  Erythrodextrin,  (C12H2()Oi0)lg  +  H20,  or  (C^H^O^)^. 
((  '^.HjjO,,),  which  is  readily  soluble  in  water  and  gives  with  iodine  a  reddish- 
brown  color.  Erythrodextrin  is  converted  into  (3)  Achroodextrin,  (C12H20O1())6 
+  H20,  or  (C^H^Oio^.C^H^On,  which  is  likewise  very  soluble,  tastes  slightly 
sweet,  but  gives  no  coloration  with  iodine.  Achroodextrin  now  breaks  up 
into  (4)  Isomaltose,  which  through  change  in  configuration  is  transformed  to  its 
isomere  (5)  Maltose. 

Products  similar  to  these  are  formed  by  the  various  diastatic  ferments  in 
the  body,  and  in  addition  also  some  dextrose.  Ptyalin2  acts  rapidly  on  starch, 
producing  dextrin  and  maltose,  butvery  little  dextrose.  Amylopsin,  from  the 
pancreas,  acts  still  more  rapidly  than  ptyalin,  and  with  the  production  of  con- 
siderable dextrose.  The  diastatic  ferment  of  intestinal  juice  acts  very  slowly 
on  starch,  forming  dextrin,  maltose,  and  a  little  dextrose,  while  the  ferment  in 
blood-serum  likewise  acts  slowly  but  with  complete  transformation  of  all  the 
maltose  and  dextrin  formed,  into  dextrose. 

The  above  facts  lead  Hamburger  to  suggest  that  the  diastatic  ferments  of  the  body 
consist  of  mixtures,  in  different  proportions,  of  diastase,  which  firms  dextrin  and  maltose 
from  starch,  and  of  glucase,  which  converts  these  into  dextrose.  This,  however,  is  merely 
an  hypothesis,  and  glucase  has  never  been  prepared.  The  vegetable  diastase  is  not  iden- 
tical with  that  found  in  the  body.  Tims  ptyalin,  like  cmulsin.  breaks  up  salicin  into  sali- 
cylic alcohol  and  dextrose,  of  which  action  vegetable  diastase  is  incapable.  But  ptyalin, 
again,  is  not  identical  with  emulsin,  for  it  will  not  act  on  amygdalin. 

The  subcutaneous  injection  of  solutions  of  achroodextrin,  erythrodextrin,  anil  amylo- 
dextrin  results  in  their  partial  elimination  in  the  urine,  the  rest  being  burned.3 

Glycogen,  or  Animal  Starch.— Recent  investigations  have  shown  that  in 
all  the  particulars  of  diastatic  decomposition  glycogen  is  identical  with  vege- 
table starch.4  Glycogen  is  soluble  in  water,  giving  an  opalescent  fluid.  The 
blood  has  a  normal  composition  which  does  not  greatly  vary.  After  a  hearty 
meal  excess  of  fat  is  deposited  iu  fatty  tissue,  excess  of  proteid  in  the  muscular 

1  Lintner  und  Dull  :    Berichte  der  dt  »/.«•/,<  »  cIk  nu.-rlien  Gesellschaft,  1893,  Bd.  26,  S.  2533. 

2  See  Hamburger:  Pfluga'i  Arckiv,  1895,  Bd.  60,  S.  573. 

8  Yoit,  )■'.     Deutsche*  Archivfiir  klinische  Median,  Bd.  -13.  S.  523. 
4  Kiil/.  and  Vogel  :  Zetochrift  fur  Biologie,  Is'.'."),  Bd.  31,  S.  108. 


THE   CHEMISTRY   OF   THE   ANIMAL   BODY.  567 

tissue,  while  excess  of  sugar  is  stored  iu  the  muscles  and  especially  in  the  liver- 
cells  in  the  less  combustible  and  less  diffusible  form  of  glycogen.  About  one- 
half  of  the  total  quantity  of  glycogen  is  found  in  the  muscles,  the  remainder 
in  the  liver,  where  it  may  even  amount  to  40  per  cent,  of  the  dry  solids. 
When  the  blood  becomes  poor  in  sugar,  the  store  of  glycogen  is  drawn  upon  to 
such  an  extent  that  in  hunger  the  body  loses  the  larger  part  of  its  glycogen. 
Muscular  work  likewise  causes  the  rapid  conversion  of  glycogen  into  sugar. 
The  sources  of  glycogen  are  certain  ingested  carbohydrates,  and  also  the 
dextrose  derived  from  proteid.  If  large  quantities  of  proteid  be  fed, 
glycogen  may  be  stored.  If  dextrose,  levulose,  or  galactose  (or  anything 
which  produces  these,  e.  g.  cane-sugar,  maltose,  milk-sugar)  be  fed,  there 
may  be  a  direct  conversion  of  these  sugars  into  glycogen.  Cremer  maintains 
that  the  pentoses  are  burned  in  the  body,  but  are  only  indirectly  glycogen- 
producers  in  the  sense  of  sparing  other  sugar  from  destruction,  which  may 
be  used  to  form  glycogen. 

Dextrins. — These  have  been  described  under  starch. 

H    H    OHH 

^-Glucuronic  Acid,  or  Glycuronic  Acid,  HOOC  C     C      C     C    C  HO. 

OH  OHH  OH 
— Obtained  by  reducing  d-saccharic  acid  with  nascent  hydrogen.  After  feed- 
ing chloral  hydrate,  naphthalin,  camphor,  terpentine,  phenol,  ortho-nitrotoluol, 
and  other  bodies,  they  appear  in  the  urine  (usually  having  been  first  converted 
into  alcohol)  in  combination  with  glycuronic  acid.  Urochloralic  acid,  naphthol- 
glycuronic  acid,  campho-glycuronic  acid,  terpene-glycuronic  acid,  etc.,  all  rotate 
polarized  light  to  the  left.  It  seems  that  these  ingested  substances  unite  in  the 
body  with  the  aldehyde  group  of  dextrose,  at  the  same  time  protecting  all  but 
one  group  of  the  dextrose  molecule  from  further  oxidation  (Fischer).  Glycu- 
ronic acid,  which  is  easily  separated  by  hydrolysis  from  its  aromatic  combina- 
tion, itself  rotates  polarized  light  to  the  right,  reduces  alkaline  copper  solutions, 
and  might  be  confounded  with  dextrose  except  that  it  does  not  ferment  with 
yeast.  Glycuronic  acid  is  likewise  found  in  the  urine  after  administration  of 
curare,  morphine,  and  after  chloroform-narcosis,  perhaps  paired  with  aromatic 
bodies  formed  in  the  organization. 

Combustion  in  the  Cell,  in  General. — Experiments1  show  that  taking 
the  proteid  decomposition  in  the  starving  dog  as  1,  it  is  necessary  to  feed  three 
to  four  times  that  amount  of  proteid  taken  alone  in  order  to  attain  nitrogenous 
equilibrium,  1.6  to  2.1  times  that  amount  of  proteid  when  i'ed  with  fat,  and  1  to 
1.2  times  that  amount  when  led  with  carbohydrates.  The  physiological  proteid 
minimum  is  in  these  eases  never  less  than  the  amount  required  in  starvation. 
Only  after  feeding  gelatin  with  proteid  may  the  proteid  led  be  below  the 
amount  decomposed  in  starvation.  The  above  show-  wliai  is  well  known,  that 
sugar  spares  proteid  from  decomposition   more  than  I'at  does.      E.  Voil  J  States 

1  E.  Voit  and  Korkunoff:  Zetisehrifl  fir  Biologic,  1895,  Bd.  32,  S.  117. 

2  Op.  cit,  S.  128  and  135. 


568  AN   AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

these  two  propositions:  (1)  The  part  played  by  these  several  food-stuffs  in  the 
total  metabolism  depends  on  the  composition  of  the  fluid  feeding  the  cell. 
The  greater  the  amount  of  one  of  these  food-stuffs,  the  greater  its  decompo- 
sition and  the  less  the  decomposition  of  the  others,  so  long  as  the  total  decom- 
position sutlers  no  change.  (2)  The  several  food-stufls  do  not  act  wholly  on 
account  of  their  quantity  in  the  fluid  surrounding  the  cell,  but  especially  accord- 
ing to  the  chemical  affinity  of  the  cell-substance  for  them  individually.  First 
in  this  regard  comes  proteid,  then  carbohydrates,  and  lastly  fat. 

The  excessive  proteid  decomposition  in  diabetes  is  due  to  the  non-combus- 
tion of  the  proteid  protecting  sugars,1  and  the  same  is  in  part  true  in  fever, 
where  a  small  supply  of  carbohydrates  reaches  the  blood.2  Dextrose  and 
levulose  weight  for  weight  have  equal  value  in  protecting  proteid  metabolism.3 

For  further  discussion  of  carbohydrates  in  the  body  see  under  the  indi- 
vidual sugars,  and  under  Fat  in  the  Body. 

Benzol  Derivatives  or  Aromatic  Compounds. 
The  aromatic  compounds  are  characterized  by  a  configuration  in  which  six 
atoms  of  carbon  are  linked  together  in  a  circle  called  the  benzol  ring.     The 
type  of  this  is  benzol,  a  hydrocarbon  found  in  coal-tar  and  having  the  formula, 

H  1 

H— C  C— H 

H— C  C— H 

\    //  °\/' 

C  4 

H 

The  hydrogen  atoms  may  be  substituted  by  others,  substitution  of  one  OH 

group,    for   example,    forming    phenol,   C6H5 — OH.     If,  however,  two   OH 

groups  are  substituted,  three  different   bodies,  corresponding  to  the  different 

arrangements  on  the  ring,  become  possible.     If  the  two  OH  groups  occupy 

the  positions   1   and   2  the  substance  is  ortho-dioxy benzol;  if  1  and  3,  meta- 

dioxybenzol ;  and  if  1  and  4,  ^am-dioxybenzol. 

It  is  possible  to  convert  bodies  of  the  fatty  series  into  those  of  the  aro- 
matic. Acetylene  passed  through  red-hot  tubes  yields  benzol.  On  the  other 
hand,  aromatic  bodies  may  be  converted  into  those  of  the  fatty  series.  If 
phenol  in  aqueous  solution  be  subjected  to  electrolysis  by  an  alternating  cur- 
rent under  which  cireumstanccs  hydrogen  and  oxygen  are  alternately  liberated 
on  the  same  pole,  the  effect  of  this  intermittent  oxidation  and  reduction  is  to 
break  up  the  phenol  into  caproic  acid,  and  finally,  after  passing  through  acids 
of  lower  carbon  contents,  into  carbonic  acid  and  water. 

The    aromatic    compounds    found    in  the    urine  are    normally  exclusively 

1  Lu-k  :   Zetischriftfur  Biolopie,  1890,  Bd.  27,  S.  459.  2  May:   Ibid.,  1894,  Bd.  30,  S.  1. 

3  De  Renzi  mid  Realis:  VI I.  Congress/iir  innere  Medizin,  1S96. 


THE   CHEMISTRY  OF   THE   AX  IMA  I    BODY.  569 

derived  from  the  products  of  proteid   putrefaction   in  the   intestines.     It   is 
admitted  that  neither  fats  nor  carbohydrates  play  any  part  in  their  formation. 

Benzol,  C6H6. — This  body  if  fed  is  absorbed  and  afterward  converted  into  oxybenzol 
or  phenol,  with  subsequent  behavior  similar  to  phenol. 

Phenol  (Carbolic  Acid,  Oxybenzol,  Phenyl-hydroxide),  C6H5OH. — 
This  is  an  aromatic  alcohol.  A  5  per  cent,  solution  precipitates  proteid,  and  a 
much  weaker  solution  produces  irritation  of  the  tissues,  and  especially  those 
of  the  kidney,  where  its  excretion  takes  place.  It  is  strange  that  a  strong 
antiseptic  like  phenol  should  be  a  normal  product  of  proteid  putrefaction. 
Phenol  is  obtainable  from  tyrosin,  by  processes  of  cleavage  and  oxidation  (see 
Tyrosin),  and  in  the  intestinal  canal  is  probably  derived  from  tyrosin.  A 
small  amount  of  the  phenol  ordinarily  absorbed  is  converted  by  the  organism 
into  pyrocatechin,  a  dioxybenzol.  These  two  substances  are  found  in  normal 
urine  in  ethereal  combination  with  sulphuric  acid,  C6H5O.SO,,.OH  (or  as  an 
alkaline  ethereal  sulphate).  This  synthesis,  accomplished  by  the  union  of  the 
phenol  and  sulphuric  acid  with  loss  of  water,  has  been  obtained  by  electrolysis, 
using  alternating  electric  currents.1  If  phenol  be  administered  in  more  than 
a  very  small  amount,  hydroquinone  likewise  appears  in  the  urine,  paired  like 
the  others  with  sulphuric  acid,  and  should  the  phenol  administered  exceed  at 
any  time  the  available  sulphate,  it  forms  to  a  certain  extent  a  synthesis  with 
glycuronic  acid,  and  so  combined  appears  in  the  urine. 

Phenol  gives  with  Millon's  reagent  (mercuric  nitrate  in  nitric  acid  with  some  nitrous 
acid)  a  brilliant  red  coloration.  This  is  given  by  all  bodies  having  an  hydroxyl  group  on  the 
benzol  ring,  of  which  substance  tyrosin  may  be  mentioned  as  an  example.  It  is  likewise 
given  by  proteid,  slowly  in  the  cold,  more  rapidly  on  warming,  and  this  fact  together 
with  the  cleavage  putrefactive  products  has  given  foundation  to  the  belief  that  the  oxy- 
benzol ring  exists  preformed  in  the  proteid  molecule. 

Pyrocatechin,  C6H4(OH)2. — This  is  ortho-dioxybenzol.  For  its  forma- 
tion see  under  Phenol. 

Hydroquinone,  C6H4(OH)2. — Para-dioxy benzol.  Found  in  the  urine 
especially  in  cases  of  carbolic-acid  poisoning  (see  Phenol).  If  such  urine  be 
shaken  in  the  air,  it  is  turned  black,  owing  to  the  oxidation  of  hydroquinone 

/? 

to  quinone,  C6H/    |  . 

p-Cresol,  C6H4.OH.CH3. — This  is  a  product  of  intestinal  putrefaction,  and  is 
derived  from  tyrosin  (which  see).     It  is  found  in  the  urine  as  an  ethereal  sulphate. 

Benzoic  Acid,  C6H6COOH. — Salts  of  this  acid  and  analogous  bodies 
arc  found  especially  in  plants.  In  the  urine  of  herbivora  therefore  is  found  a 
considerable  amount  of  hippuric  <i<-i<l,  COOH.CH2.NH.CO.C6H8,  the  com- 
bination of  benzoic  acid  and  glycocoll  (sec  Glycocoll,  p.  537).  On  (reding 
phenyl-acetic  acid,  C6H6CH2COOH,  phenaceturic  acid,  COOHjCHg. NH.- 
CO.CH2.C6H6,  appears  in  the  urine,  while  the  higher  benzyl  acids,  such  as 
phenyl-propionic  add,  sutler  the  oxidation  of  the  side  chain  in  the  ho.lv,  and 

1  Drechsel :  Journal  fin-  praktUehe  Chemie,  Bd.  29,  ]>.  229  :  abstr.  Jahresberichi  uber  Thiercfu 

1884,  S.  77. 


570  AN    AMERICAN    TEXT-BOOK    OF    PHYSIOLOGY. 

ordinary  hippuric  acid  is  formed.  After  eating  apple-parings  and  other  vege- 
table substances,  hippuric  acid  is  found  in  human  urine.  It  is  further  stated 
thai  phenyl-aeetic  acid  and  phenyl-propionic  acids  are  normal  products  of 
proteid  putrefaction,  though  in  very  small  quantities  ;  hippuric  acid  and  phen- 
aceturic  acid  must  therefore  be  constantly  present  in  traces  in  human  urine. 
Hippuric  acid  is  split  into  its  constituents  by  hydrolysis  through  the  action  of 
the  Micrococcus  ureoe. 

p-Oxyphenyl-acetic  Acid,  0,  H,.OH.CH2COOH. — This  is  a  product  of 
the  intestinal  putrefaction  of  proteid  and  of  tyrosin  (which  see).  It  occurs 
in  the  urine  either  paired  with  sulphuric  acid  or  as  an  alkaline  salt  of  oxyphenyl- 
acetic  acid.1 

p-Hydrocumaric  Acid,  Ct.H4.OH.C2H4COOH. — This  second  oxy-  acid  is 
likewise  derived  from  proteid  and  tyrosin  (which  see)  putrefaction.  Its  occur- 
rence in  the  urine  is  similar  to  the  above  oxy-  acid. 

Tyrosin,  Amido-hydrocumaric  Acid,  ^-Oxyphenyl-amido-propionic 
Acid,  C6H4.OH.C2H3NH2COOH. — Tyrosin  is  a  constant  product  of  the  putre- 
faction of  all  proteid  bodies  (except  gelatin),  and  is  therefore  found  in  cheese. 
It  may  be  formed  in  large  quantities  by  boiling  horn-shavings  with  sul- 
phuric acid.  Leucin  is  always  formed  whenever  tyrosin  is.  Tyrosin  forms 
characteristic  sheaf-shaped  bundles  of  crystals.  All  the  aromatic  bodies  thus 
far  described  have  been  eliminated  in  the  urine  with  their  benzol  nucleus 
intact.  Tyrosin,  however,  may  be  completely  burned  in  the  body.  This 
seems  to  be  because  of  the  presence  of  the  amido-  group  on  the  side  chain,  for 
phenyl-amido-propionic  acid  is  likewise  destroyed.  Tyrosin  is  found  in  the 
urine  in  yellow  atrophy  of  the  liver,  in  phosphorus-poisoning,  etc.  (see  Leucin, 
p.  o40).  Through  cleavage,  oxidation,  or  reduction,  the  following  reactions 
take  place,  phenol  being  the  final  product.2  The  substances  not  found  in  intes- 
tinal putrefaction  are  named  in  italics: 

C6H4.OH.C2H3NH2COOH  -  H2  C6H4.OH.C2H4COOH  +  NH3 

p-TIydrocumaric  acid. 

C6H4.OH.C2H4COOH  C6H4.OH.C2H5  +  C02 

p-Ethylphenol. 

C6H4.0H.C2H5  +  30  C6H4.0H.CH2C00H  -  H20 

p-Oxyphenyl-acetic  acid. 

C6H4.0H.CH2C00H  C6H4.0H.CH,  +  CO, 

/<-«  resol. 

C6H4.OH.CH3  +  30  CJLOHCOOH  +  H20 

p-Oxybenzoic  acid. 

CeH4.0H.C!00H  C6H5OH  +  C02 

Phenol. 

It  has  never  been  shown  that  tyrosin  i-  a  normal  product  of  proteid  metabolism 
within  the  tissues.  With  leucin  it  is  a  normal  product  of  pancreatic  diges- 
tion (see  p.  540). 

Homogentisic  Acid,  Dioxyphenyl-acetic  Acid,  Hydroquinone-acetic  Acid  — 
Tlii^  i.-  found  in  the  urine  in  alcaptonuria.     Feeding  tyrosin  in  this  disease  increases  the 

1  Baumann:  Zeitsehriftfur  physiologische  Chemie,  1886,  Bd.  10,  S.  125. 

J  Baumann  :  Berichte  der  deidschen  ehemisehen  Gesellschaft,  1879,  Bd.  12,  S.  1450. 


THE   CHEMISTRY  OE  THE  ANIMAL   BODY.  571 

amount  of  homogentisic  acid.     It  may  arise  from  the  reduction  and  oxidation  of  tyrosin 
according  to  the  following  reaction:1 

+  H2 


OH/      \  NH3+C02  +  2H20 

+  502  = 

'oh 


CH2CHNH2COOH  CH2COOH 


Pyridin.— This  hody  has  the  accompanying  formula,  one  of  the  CH  groups  in  benzol 
H 
C 

HC      CH 

being  substituted  by  N :  ||    •     When  pyridin  is  fed,  methyl-pyridin   ammonium 

HC      CH 

V 

hydroxide,  OH.CH3.NC5H5,  is  excreted  in  the  urine.2  This  is  another  case,  besides  those 
of  selenium  and  tellurium,  of  methylation  in  the  body. 

H      H 

C      C 

HC      C      CH 
Chinolin. — The  accompanying  formula  illustrates   the   composition 

HC      C      CH 

N       C 
H 
of  this  body.     Several  of  the  methyl-chinolins  burn  readily  in  the  body.3 

Cynurenic  Acid,  C9H5N.OH.COOH.—  This  is  oxychinolin  carbonic  acid ;  it  is  found 
normally  in  dog's  urine,  being  derived  from  proteid  in  amounts  proportional  to  proteid 
metabolism.  It  is,  however,  not  derived  from  the  metabolism  of  gelatin,4  a  body  which 
does  not  yield  the  aromatic  chain. 

Indol,  or  Benzopyrol,  C8H7N. — The  source  of  indol  is  surely  from 
proteid  putrefaction;  it  may  also  be  obtained  by  melting  proteid  with  potash. 

H  H 

C  C 

//  \  /\  //  \  y\ 

HC         C         CH  HC         C         COH 

I  II  II  I  II  II 

HC         C         CH  HC         C         CH 

^/\/  % /\/ 

C         N  C         N 

H        H  H        H 

Indol.  Indoxyl. 

After  its  absorption  it  receives  an  oxy-  group  ju>t  as  benzol  docs,  and  like 
benzol  pairs  with  sulphuric  acid  with  the  loss  of  a  molecule  of  water,  and 
appears  as  ethereal  sulphate  in  the  urine.  In  preparing  indol  from  feces  the 
fecal  odor  clings  to  it.      Pure  indol,  however,   has  no  smell.      An   alcoholic 

'Enibden:  Zeittehrift fur  physiologiscke  Chemie,  189:2,  I5d.  17,  8.   182. 

2  His:  Archiv fur  exper.  Pathologie  wad  Pharmafcologie,  1887,  I'«d.  22,8.263. 

3  Cohn:  Zeiischrift  fur  phymlogische  Chemie,  1804,  I'.d.  20,  S.  210. 

*  Mendel  and  Jackson  :  American  Journal  of  Physiology,  1899,  vol.  ii.  p.  1. 


572  AN  AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

solution  of  indol  mixed  with  hydrochloric  acid  colors  fir-wood  cherry-red. 
If  urine  be  mixed  with  an  equal  volume  of  hydrochloric  acid,  chloroform 
added,  and  then  gradually  an  oxidizing  agent  (chloride  of  lime),  any  indoxyl- 
sulphuric  acid  present  will  be  oxidized  to  indigo-blue,  which  gives  a  blue  color 
to  the  chloroform  in  which  it  dissolves. 

Skatol,    or    ,3-Methyl    Indol,    C8H6CH3NH. — The    history   of    skatol, 

H 
C 
//  \    /\ 

HC         C         CCH3 
I  II  II        , 

HC         C         CH 

%  /\/ 
C         N 
H         H 

Skatol. 

is  the  same  as  that  of  indol.  Its  source  is  from  proteid  putrefaction  ;  after  ab- 
sorption it  unites  with  an  oxy-  group,  and  the  skatoxyl  thus  produced  pairs  with 
sulphuric  acid,  and  appears  in  the  urine  as  ethereal  skatoxyl-sulphuric  acid. 

CH3 

Epinephrin.— C6H4  ^C.CHOH.CO.C6H3(OH)2.     The  above  is  the 

XNH7 
formula  for  epinephrin,  the  active  principle  of  the  suprarenals,  as  proposed 
by  Abel.1     Abel  has  formed  several  distinct  salts  of  this  pyrrol  base.     Of 
the  sulphate  of  epinephrin,  only  0.000018  gram  per  kilogram  of  dog  causes 
a  sharp  rise  in  blood-pressure. 

Aromatic  Bodies  in  the  Urine. — There  have  been  named  above  as 
appearing  in  normal  human  urine  the  ethereal  sulphates  of  phenol,  jo-cresol, 
pyroeatechin,  indoxyl,  skatoxyl,  hvdroparacumaric  acid,  and  oxyphenyl-acetic 
acid,  of  which,  however,  the  last  two  appear  likewise  as  their  salts  without 
being  combined  with  sulphuric  acid.2  These  are  derived  from  proteid  putre- 
factive products  formed  almost  entirely  in  the  large  intestine  (see  p.  545), 
which  are  partially  absorbed  and  partially  pass  into  the  feces.  The  amount 
of  ethereal  sulphate  in  the  urine  gives  an  indication  of  the  amount  of  intes- 
tinal putrefaction.  It  does  not  disappear  in  starvation,  mucin  and  nucleo- 
proteid  of  bile  and  intestinal  juice  furnishing  material.3  If  the  intestinal 
tract  be  treated  so  as  to  make  it  antiseptic,  the  ethereal  sulphates  disappear 
from  the  urine.4  Diarrhoea  likewise  decreases  their  amount,  obviously  from 
the  short  time  given  for  putrefaction.  The  synthesis  between  the  aromatic 
bodies  and  sulphuric  acid  probably  occurs  in  the  liver.  The  liver  and  the 
kidney  both   have  the  power  of  combining  with  a  considerable  amount  of 

1  ZeitsehriftJUr  phyiriologische  Chemie,  1899,  Bd.  28,  S.  318. 

1  Baumann:  Zeitschrifi  fib-  phi/xiolni/iarhr  (Vn-mir.  ism;,  Bd.  10,  S.  125. 

s  Von  Noorden  :   Pathologic  des  Stoffwechsels,  1893,  S.  163. 

*  Baumann  :  Op.  cit.,  S.  129. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  573 

indol  and  phenol,  holding  them  until  the  requisite  synthesis  between  them 
and  .sulphuric  acid  occurs,  and  thereby  rendering  them  non-poisonous.1 

Inosit. — This  is  the  hexatomic  phenol  of  hexahvdrobenzol,  C6Hc(OH)6. 
It  was  long  mistaken  for  a  carbohydrate.  It  has  been  found  in  muscle,  liver, 
spleen,  suprarenals,  lungs,  brain,  and  testicles ;  likewise  in  plants,  in  unripe 
peas  and  beans.  After  drinking  much  water  it  may  be  washed  out  in  the 
urine,  and  perhaps  for  this  reason  is  often  found  in  the  voluminous  urine  of 
the  diabetic.  When  fed  it  is  burned ;  also  by  the  diabetic.  Its  origin  is 
unknown. 

Substances  of  Unknown  Composition. 

Coloring  Matters  in  the  Body. 

Haemoglobin,  C712HU30N2UFeS2O245  (Zinoffsky's  formula  for  haemoglobin  in  horse's 
blood). — Haemoglobin  is  found  in  the  red  blood-corpuscle,  probably  in  chemical  union 
with  the  stroma.2  United  with  oxygen  it  forms  oxyhaenioglobin,  which  gives  the  scarlet 
color  to  arterial  blood ;  haemoglobin  itself  is  darker,  more  bluish,  and  therefore  venous 
blood  is  of  a  less  brilliant  red.  Methods  for  preparing  oxyhemoglobin  crystals  are 
numerous,  but  all  depend  on  getting  the  haemoglobin  into  solution.  If  the  corpuscles 
in  cruor  be  washed  witli  physiological  salt-solution,  and  then  treated  with  distilled  water, 
the  HbO  will  be  dissolved;  on  shaking  with  a  little  ether  the  stroma  will  likewise  dis- 
solve; after  decantation  and  evaporation  of  the  ether,  at  the  room's  temperature,  the 
solution  is  cooled  to  — 10°  and  a  one-fourth  volume  of  alcohol  at  the  same  temperature 
added;  after  a  few  days  rhombic  crystals  of  oxyhaemoglobin  may  be  collected,  redis- 
solved  in  water,  and  re  precipitated  for  purification.  The  crystals  may  be  dried  in  vacuo 
over  sulphuric  acid.  Once  dry  they  may  be  heated  to  100°  without  decomposition,  but 
in  aqueous  solution  they  are  decomposed  at  70°  into  a  globulin  and  haematin.  the  latter 
having  a  brown  color.  This  difference  in  color  gives  the  distinction  between  "rare  "  and 
"well-done"  roast-beef.  Gastric  and  pancreatic  digestion  likewise  converts  oxyhaemo- 
globin into  a  globulin,  which  may  be  absorbed,  and  haematin,  which  passes  into  the  feces. 
Haemoglobin  is  without  doubt  formed  in  the  body  from  simple  proteids  by  a  synthetic 
process,  (for  further  information  see  pp.  529  and  574,  and  likewise  under  the  sen  ion 
on  Blood.) 

CO-Haemoglobin  (see  p.  51 7). 

NO-Hsemoglobin  (see  p.  512). 

Methsemoglobin.— This  is  found  in  blood-stains,  and  may  be  considered  as  oxyhaemo- 
globin which  has  undergone  a  chemical  change  whereby  some  of  the  loosely  combined 
oxygen  has  been  liberated.3 

Haematin,  C32H;!2N40.,Fe. — This  is  a  cleavage-product  of  haemoglobin  in  the  presence 
of  oxygen.  (See  above,  under  Haemoglobin).  It  is  not  itself  a  constituent  of  the  body. 
It  is  insoluble  in  dilute  acids,  alcohol,  ether,  or  chloroform,  but  is  soluble  in  alkalies  or  in 
aeiditied  alcohol  or  ether,  showing  characteristic  absorption-bands.  If  a  little  dry  blood 
be  placed  on  a  microscope  slide  with  NaCl  and  moistened  with  glacial  acetic  acid,  and 
wanned,  characteristic  brown  microscopic  crystals  of  licemin,  I '  1 1  N  ,  Fe(  I  1 1 1  '1.  crystallize 
out.  If  these  crystals  and  the  spectroscopic  test  be  obtained,  one  can  be  absolutely  posi- 
ti\  c  of  the  presence  of  Mood. 

Haemochromogen,  (VJT^NgFe.^. — This  substance  has   the  same  composition   as 
haematin,  only  it  contains  less  oxygen.4    If  reduced  haemoglobin  be  heated  in  scaled  tubes 
with  dilute  acids  or  alkali  in  absence  of  oxygen,  a  purple-red  compound  is  produced  called 
1  Herter  and  Wakeman :  Journal  of  Experimental  Medicine,  1899,  vol.  iv.  p.  307. 
3  Read  .Stewart,  G.  N.:  Journal  of  Physiology,  1899,  vol.  xxiv.  p.  238. 

3  Zeynek:  Archivfur  Physiologic,  1899.  S.  460. 

4  Zeynek:  Zeilschrift  fiir  physiologische  Chemie,  1898,  Bd.  25,  S.  492. 


7u  [  AN    AMERICAN    TEXT-BOOK    OF  PHYSIOLOGY. 

haemochromogen,  which  is  a  crystallizable  cleavage-product  of  haemoglobin.  According 
to  Hoppe-Seyler  the  oxygen  in  oxyhaemoglobin  is  bound  to  the  haemochromogen  group. 
Haemochromogen  treated  with  a  strong  dehydrating  agent  is  converted,  with  elimination 
of  iron,  into  Jioematoporphyrin,  Ci6H,8N.,03,  an  isomer  of  bilirubin.     Haematoporphyrin 

is  said  to  occur  in  normal  urine.1  Haematoporphyrin  treated  with  nascent  hydrogen  is 
converted  into  a  body  believed  to  be  identical  with  hydro-  or  urobilirubin.  Analogous  to 
this  is  the  work  of  the  liver  in  the  body,  manufacturing  the  biliary  coloring  matter  from 
haemoglobin,  and  retaining  the  separated  iron  for  the  synthesis  of  fresh  haemoglobin 
(see  p.  5i29).  Hcematoidin,  found  in  old  blood-stains,  is  believed  to  be  identical  with 
bilirubin. 

The  Bile-pigments. — The  ordinary  coloring  matter  of  yellow  human  bile  is  bilirubin, 
C;JI:iBN406.  The  next  higher  oxidation-product  is  the  green  bit  inn  I  in,  C32H36NtOfe, 
which  is  the  usual  dominant  color  in  the  bile  of  herbivora.  These  coloring-matters  and 
others  derived  from  them  have  been  found  in  gall-stones.  Jolles2  gives  the  following 
products  of  the  oxidation  of  bilirubin: 

Bilirubin  (red)  t'16HI8X203; 

Biliverdin  (green)  C16HlsN2Oi; 
Bilicyanin  (blue)  ? 

— - —     (violet)  ? 

(red)  ? 

(brown)  ? 

Bilixanthin  (brownish-yellow)        C16H18N20». 

If  nitric  acid  containing  a  little  nitrous  acid  be  added  to  a  solution  ol  bilirubin,  a  play  of 
colors  is  observed  at  the  juncture  of  the  two  fluids,  undoubtedly  depending  upon  various 
st; i -es  of  oxidation.  Above  is  a  ring  of  green  (biliverdin),  then  blue  and  violet  (bilicya- 
nin), red,  yellowish-brown  (bilixanthin).  Bilixanthin  (=  choletelin)  is  the  highest  oxida- 
tion-product.    The  above  is  known  as  Gmelins  test.3 

If  bilirubin  or  biliverdin  is  subjected  to  the  action  either  of  nascent  hydrogen  or 
of  putrefaction  it  is  reduced  to  hydrobilirubin,  C32HuN407.  This  substance  is  therefore 
formed  in  the  intestinal  tract,  is  in  part  absorbed,  and  appears  in  the  urine,  where  it  is 
called  urobilin,  though  the  two  are  identical.  Urobilin  gives  a  yellowish  coloration  to  the 
urine.  Injection  into  the  blood-vessels  of  distilled  water,  ether,  chloroform,  the  biliary 
salts,  or  arsenuretted  hydrogen,  produces  a  solution  of  the  red  blood-corpuscles  and  conver- 
sion of  haemoglobin  into  biliary  coloring  matters  which  are  thrown  out  in  the  urine.  Bili- 
rubin, biliverdin,  and  bilicyanin  give  characteristic  spectra. 

Melanins. — Under  this  name  are  classed  the  pigments  of  the  skin,  of  the  retina,  and 
of  the  iris.  In  melanosis  and  kindred  diseases  they  are  deposited  in  black  granules. 
Abel  and  Davis1  prepared  pure  pigment  from  the  skin  of  the  negro  and  find  that  it  con- 
tains no  iron  and  1.5  per  cent,  of  sulphur.  These  pigments  arise  from  proteid.  On 
decomposition  they  yield  two  melaninic  acids.5 

Tryptophan. — This  is  said  to  be  a  cleavage-product  of  hemipeptone  in  tryptic  diges- 
tion ; 6  it  gives  a  red  color  with  chlorine  and  a  violet  color  with  bromine,  due  to  halogen- 
addition  compounds. 

Lipochromes. — These  include  lutein,  the  yellow  pigment  of  the  corpus  luteum,  of 

1  Gar  rod:  Journal  of  Physiology,  1894,  vol.  17,  p.  348. 

2  Pilii./.rs  Archiv,  1899,  Bd.  75,  S.  446. 

5  For  a  delicate  modification  of  this  test  see  Jolles:  Zeitschrift  fur  physiologische  Chemie,  1895, 
Bd.  20,  S.  461. 

4  Journal  of  Experimental  Medicine,  1896,  vol.  i.  p.  361. 
1  . 1  ones:  American  Journal  of  Physiology,  1899,  vol.  ii.  p.  380. 
delmann:  Zeitschrift  fur  Biologie,  1890,  Bd.  26,  8.  491. 


THE   CHEMISTRY   OF   THE   ANIMAL   BODY.  575 

blood-plasma,  butter,  egg-yolk,  and  of  fat;  likewise  visual  purplt  of  the  retina,  which  is 
bleached  by  light,  Solutions  of  the  pure  visual  purple  from  rabbits  or  dogs  become  clear 
as  water  on  exposure  to  light.1 

Cholesterin. 

Cholesterin,  C27H45OH. — This  is  found  in  all  animal  and  vegetable  cells  and  in  the 
milk.2  It  is  especially  present  in  nervous  tissue  and  in  blood-corpuscles.  It  is  excreted 
through  the  bile  and  through  the  intestinal  wall.3  In  the  blood-plasma  it  is  present  as 
an  ester  combined  with  oleic  and  palmitic  acids,  while  in  the  corpuscle  it  occurs  as  simple 
cholesterin.*  It  may  be  prepared  by  dissolving  gall-stones  in  hot  alcohol,  from  which 
solution  the  cholesterin  crystallizes  on  cooling  in  characteristic  plates.  It  is  insoluble  in 
water  or  acids,  but  soluble  in  the  biliary  salts,  ether,  and  hot  alcohol.  Tt  is  probably  not 
absorbed  by  the  intestinal  canal.  In  human  feces  stercorin  appears  instead  of  choles- 
terin.5 This  stercorin  (the  koprosterin  of  Bondzynski)  is  a  dihydrocholesterin,8  (\,7II,;OH, 
and  is  the  result  of  putrefactive  change.7  Cholesterin  feels  like  a  fat  to  the  touch, 
but  is  in  reality  a  monatomic  alcohol.  With  concentrated  sulphuric  acid  it  yields  a 
hydrocarbon,  cholesterilin,  C26H4!„  coloring  the  sulphuric  acid  red  (Salkowski's  reaction  i. 
Iso-cholesterin,  an  isomere,  is  found  combined  as  an  ester  with  fatty  acid  in  wool-fat  or 
lanolin.     The  physiological  importance  of  cholesterin  is  unknown. 

The  Proteids. 

Consideration  of  the  proteids  from  a  purely  chemical  standpoint  is  impos- 
sible, for  their  composition  is  unknown.  There  exist  only  the  indices  of  com- 
position furnished  by  the  products  of  cleavage  and  disintegration.  Bodies  at 
present  classed  as  individuals  may  sometimes  be  shown  to  be  identical,  with 
characterizing  impurities.  It  remains  for  the  chemist  to  do  for  the  proteid 
group  what  Emil  Fischer  with  phenyl-hydrazin  has  accomplished  for  the 
sugars. 

As  a  characteristic  proteid,  egg-albumin  may  be  mentioned.  Proteid  forms 
(after  water)  the  largest  part  of  the  organized  cell,  and  is  found  in  all  the 
fluids  of  the  body  except  in  urine,  sweat,  and  bile.  Proteid  contains  carbon, 
hydrogen,  nitrogen,  oxygen,  sulphur,  sometimes  phosphorus  and  iron. 

General  Reactions. — A  neutral  solution  of  proteid  (with  the  exception  of 
the  peptones  and  proteoses)  is  partially  precipitated  on  boiling,  and  is  quite 
completely  precipitated  on  careful  addition  of  an  acid  (acetic)  to  the  boiling 
solution.  Proteids  are  precipitated  in  the  cold  by  nitric  and  the  other  com- 
mon mineral  acids,  by  metaphosphoric  but  not  by  orthophosphoric  acid. 
Metallic  salts,  such  as  lead  acetate,  copper  sulphate,  and  mercuric  chloride, 
precipitate  proteid;  as  do  ferro- and  ferricyanide  of  potassium  in  acetic-acid 
solution.  Further,  saturation  of  acid  solutions  of  proteid  with  neutral  salts 
(NaCl,  Na2S04,  (NH4)2S04)  precipitates  them,  as  docs   likewise   alcohol    in 

1  Kiihne  :  Zeitschrift  fur  Biologie,  1895,  Bd.  32,  S.  26. 
•Schmidt-Muhlheim:  Pfluger's  Arehiv,  1883,  Bd.  30,  S.  384. 
3  Moraczewski :  Zeitschrift  fiir  physiologische  Chemie,  1898,  Bd.  25,  S.  122. 
*  Hepner:  Pfluger'a  Arehiv,  1898,  Bd.  73,  S.  595. 

5  Flint:  American  Journal  of  Medical  Sciences,  1862. 

6  Bondzynski  and  Hnmnicke:  Zeitschrift  fur  physiologische  Chemie,  1S96.  Bd.  22,  B.  39(5. 
:  Miiller,  P.  :  Ibid.,  1900,  Bd.  29,  S.  129. 


:,7i; 


AN  AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 


Albumins 


neutral  or  acid  solutions.  Proteid  is  also  precipitated  by  tannic  acid  in  acetic- 
acid  solutions,  by  phospho-tuugstic  and  phospho-molybdic  acids  in  the  presence 
of  free  mineral  acids,  by  picric  acid  in  solutions  acidified  by  organic  acids.1 
The  precipitation  of  proteid  is  also  accomplished  by  nucleic  acid,  taurocholic 
acid,  and  chondroitic  sulphuric  acid  in  acid  solutions. 

Of  the  eohr-readions  the  action  of  Millon's  reagent  has  been  described 
p.  569).  Soluble  proteids  give  the  biuret  test  (see  p.  549).  With  concen- 
trated sulphuric  acid  and  a  little  cane-sugar  a  pink  color  is  given  when  proteid 
is  present  (see  p.  544).  Proteid  heated  with  moderately  concentrated  nitric 
acid  gives  yellow  Makes,  changing  to  orange-yellow  on  addition  of  alkalies 
(xantho-proteid  reaction).  Proteid  in  a  mixture  of  one  part  of  concentrated 
sulphuric  acid  and  two  parts  of  glacial  acetic  acid  gives  a  reddish-violet  color 
(Adamkiewicz),  a  reaction  accelerated  by  heating.  Finally,  proteid  dissolves 
after  heating  with  concentrated  hydrochloric  acid,  forming  a  violet-colored 
sol  i  i  tion   ( Lieberman  n) . 

The  following,  taken  in  part  from  Chittenden,2  is  submitted  as  a  general 
classification  of  the  proteids  : 

Simple  Proteids. 
Serum-albumin ; 
Egg-albumin ; 
Lacto-albumin ; 
Mvo-albumin. 
Serum-globulin ; 
Fibrinogen  ; 
Myosin ; 
Myo-globulin  ; 
Paramyosinogeu ; 
Cell-fflobulin. 
Acid-albumin ; 
Alkali-albumin. 
Proteoses  and  Peptones. 

Coagulated  Proteids  <  '  .. 

I  Other  coagulated  proteids. 

Combined  Proteids. 
Haemoglobin  ; 
Histo-hsematins ; 
Ckromo-proteids  J   Chlorocruorin ; 
Haemerythrin ; 
Haemocyanin. 

Glyco-proteids    <   _  _  ' 

*  {  Mucoids. 

1  The  above  list  is  given  by  Plammarsten,  Physiological  Chemistry,  translated  by  Mandel, 
p.  IS. 

-  "  Digestive  Proteolysis,"  Cartwright  Lectures,  1895,  p.  30. 


Globulins 


Albuminates 


THE   CHEMISTRY   OF   THE  ANIMAL   BODY.  577 

c  Casein ; 
^  1.  Those  yielding  para-nuclein  <   Pyin  ; 

Nudeo-proteids  \  '   Vitdlin.  ^ 

o   T,  •  1V        ,  l  •     i  Nucleo-histon ; 

v  2.  Ihose  yielding  true  nuclei n  <    -  „         ,  .       ' 
J  I  Gell-nuclein. 

Phospho-glyco-proteids.     Helico-proteid. 

Albuminoids. 
Collagen  (gelatin). 
Elastin. 
Keratin  and  Neurokeratin. 

Albumins. — Bodies  of  this  group  are  soluble  in  water  and  precipitated  by  boiling,  or 
on  standing  with  alcohol.  Serum-albumin  is  the  principal  proteid  constituent  of  blood- 
plasma,  while  lacto-albumin  and  myo-albumin  are  similar  bodies  found  respectively  in 
milk  and  muscle. 

Globulins. — These  are  insoluble  in  water,  but  soluble  in  dilute  salt-solutions.  They 
are  coagulated  on  heating.  If  blood-serum  be  dialyzed  with  distilled  water  to  remove  the 
salts  present,  serum-globulin  formerly  held  in  solution  separates  in  flakes.  Fibrinogen  and 
serum-globulin  are  in  blood-plasma  and  the  lymph.  Myosin  is  the  principal  constituent 
of  dead  muscles ;  in  the  living  muscle  myosin  is  said  to  be  present  in  the  form  of  myosin- 
ogen.  Myoglobulin  in  muscle  is  akin  to  serum-globulin  in  plasma.  Paramyosinogen  in 
muscle  is  characterized  by  the  low  temperature  at  which  it  coagulates  (+47°).  Cell- 
globulin  is  also  found  in  the  animal  cell. 

The  globulins  of  vegetable  cells  are  interesting  as  having  been  obtained  in  well-defined 
crystalline  form  and  in  great  purity  of  composition.1  These  are  not  generally  coagulable 
by  heat,  and  indeed  vegetable  proteids  show  many  points  of  divergence  from  those  of  the 
animal. 

Osborne2  finds  that  solutions  of  pure  crystalline  edestine  obtained  from  plants  take  up 
hydrochloric  acid  inexact  chemical  relations,  forming  the  hydrochlorato  or  bihydrochlorate 
of  edestine.  The  simplest  formula  for  edestine  ( containing  two  atoms  of  sulphur)  which  can 
be  calculated  gives  a  molecular  weight  of  7,138,  twice  which  is  14,276.  This  latter  molec- 
ular weight  exactly  unites  with  one  molecule  of  hydrochloric  acid  to  form  edestine 
hydrochlorate.  Osborne  regards  the  many  variations  in  similar  L'  native  "  albumins  as  being 
fundamentally  caused  by  the  quantity  and  quality  of  the  acid  or  alkali  with  which  they 
unite. 

Albuminates. — If  any  of  the  above  native  animal  proteids  or  any  coagulated  proteid 
be  treated  with  an  alkaline  solution,  alkali  albuminate  is  formed.  In  this  way  the  alkali 
of  the  intestine  acts  upon  proteid.  If  hydrochloric  acid  acts  on  proteid.  there  is  a  gclatin- 
ization  and  slow  conversion  into  acid  albuminate,  a  process  accelerated  by  the  presence 
of  pepsin.  This  takes  place  in  the  stomach.  Both  alkali  and  acid  albuminates  are  in- 
soluble in  water,  but  both  are  soluble  in  dilute  acid  or  alkali,  without  loss  of  individual 
identity. 

Proteoses  and  Peptones. — These  are  bodies  obtained  from  the  digestion  of  proteids, 
through  a  process  of  hydrolysis.  They  are  non-coagulable  by  heat.  If  a  mixture  of  pro- 
teoses and  peptones  be  saturated  with  ammonium  sulphate  the  proteoses  are  said  to  be 
precipitated,  while  true  peptone  remains  in  solution.  The  chemical  identity  of  this  true 
peptone  is  still,  however,  to  be  established.  In  the  gastric  digestion  of  fibrin,  proto- 
proteose,  hetero-proteose,    and  deutero-proteose   B,  arise  as   primary  cleavage  products.8 

1  Osborne  :  Journal  of  American  Chemical  Society,  1894,  vol.  xvi.,  Nos.  9,  10;  and  other  arti- 
cles in  the  same  journal  by  the  same  author. 

2  Op.  efl.,1899,  vol.  21,  p.  48(3. 

3  Zunz,  E.  :  Zeitschrift  fiir  physiologische  Chemie,  1899,  Bd.  28,  S.  132. 

Vol..  I. — 37 


578  AN  AMERICAN    TEXT- HOOK    OF  PHYSIOLOGY. 

Fibrin  yields  a  carbohydrate  radicle  which  appears  in  deutero-proteose  B  and  subse- 
quently in  peptone  A.1    The  primary  proteoses  are  believed  to  break  np  into  secondary 

proteoses,  such  as  deutero-proteose  A  and  deutero-proteose  C.  and  perhaps  others,  and 
these  secondary  proteoses  maybe  converted  into  peptones,  although  gastric  digestion  will 
not  convert  some  deutero-proteoses  into  peptone.2  Egg  albumin  and  other  proteids 
yield  similar  products.  The  whole  process  of  proteolytic  cleavage  has  been  compared 
with  the  hydrolytic  cleavage  of  starch  into  dextrins  and  sugars.  According  to  Kiihne, 
proteid  consists  of  a  hemi-  and  an  anti-  group,  which  separate  into  distinct  hemi-  and 
anti-  bodies  in  proteolysis.  Of  the  final  products,  hemi-  and  anti-peptone,  only  the  former 
yields leucin  and  tyrosin  in  tryptic  proteolysis.  This  is  the  only  radical  difference  between 
the  two  peptones,  hence  hemi-peptone  has  never  been  isolated.  Kutscher3  denies  the 
existence  of  anti-peptone  and  shows  that  prolonged  tryptic  proteolysis  almost  completely 
transforms  proteid  into  amido  bodies. 

Coagulated  Proteids. —These  are  insoluble  in  water,  salt -solutions,  alcohol,  dilute 
acids  and  alkalies,  but  soluble  in  strong  acids  and  alkalies,  pepsin-hydrochloric  acid, 
and  alkaline  solutions  of  trypsin.  The  chemical  or  physical  change  which  is  effected  in 
coagulation  of  proteid  is  unknown. 

Combined  Proteids. — These  consist  of  proteid  united  to  non-proteid  bodies  such  as 
hgemochromogen,  carbohydrates,  and  nucleic  acid. 

Chromo-proteids. — These  are  compounds  of  proteid  with  an  iron-  or  copper-contain- 
ing pigment,  like  haemoglobin,  which  has  already  been  described.  Histohcematins  are 
iron-containing  pigments  found  especially  in  muscle.  That  which  is  found  in  muscle  is 
called  myohsematin,  and  resembles  bsemochromogen  somewhat  in  its  spectroscopic  appear- 
ance, and  is  believed  to  be  present  in  two  forms  corresponding  to  haemoglobin  and  oxyhaemo- 
globin.  It  has  been  regarded  as  an  oxygen-carrier  to  the  tissues.  Among  the  inverte- 
brates the  blood  often  contains  only  white  corpuscles  with  sometimes  a  colored  plasma. 
Thus  the  blood-serum  of  the  common  earth-worm  contains  dissolved  haemoglobin,  that 
of  some  other  invertebrates  a  green  respiratory  pigment,  chlorocruorin,  whose  charac- 
terizing component  seems  similar  to  hsematin ;  hcemerythrvn  occurs  in  the  pinkish  corpus- 
cles of  Sipunculus,  while  the  blood  of  crabs,  snails,  and  other  animals  (mollusks  and 
arthropods)  is  colored  blue  by  a  pigment,  hcemocyanin,  which  contains  copper  instead  of 
iron. 

Glyco-proteids. — These  consist  of  proteids  combined  with  a  carbohydrate.  They  are 
insoluble  in  water,  but  soluble  in  very  weak  alkalies.  On  boiling  with  dilute  mineral  acids 
they  yield  a  reducing  substance. 

Mucin*  are  found  in  mucous  glands,  goblet  cells,  in  the  cement  substance  of  epithelium 
and  in  the  connective  tissues.  Of  the  nearly  related  mucoids  may  be  named  colloid,  a  sub- 
stance appearing  like  a  gelatinous  glue  in  certain  tumors;  pseudo-mucerid,  the  slimy  body 
which  gives  its  character  to  the  liquid  in  ovarian  cysts;  and  chondro-mucoid,  found  as  a 
constituent  of  cartilage.  On  boiling  chondro-mucoid  with  dilute  sulphuric  acid  it  yields 
acid-albuminate,  a  peptone  substance,  and  chondroitic  acid.  The  last  is  a  nitrogenous 
ethereal  sulphuric  acid,  yielding  a  carbohydrate  on  decomposition,  and  found  preformed  in 
every  cartilage  *  and  in  the  amyloid  liver.5  It  is.  of  course,  not  a  proteid.  Amyloid  is 
similar  to  chondro-mucoid,  and  may  be  identical  with  it.  Tt  is  said  to  consist  of 
chondroitic  sulphuric  acid  in  combination  with  proteid.6  and  yields  proteid  and  phosphoric 
acid  on  decomposition. 

1  Pick  :  Zeitsehrifijur  •physiologwehe  Chemie,  1899,  Bd.  28,  S.  219. 

aFolin:  Ibid.,  1898,  Bd.  25,  S.  1 52. 

B  Die  Endprodukle  der  Trypsrinverdauung,  Strassburt;,  1899. 

4  Morner:  Zeitschriftfur  physiologische  Chemie,  1895,  Bd.  20,  S.  357. 

b  Odili :  Archiv  fiir  exper.  Pathologic  und  Pharmakologie,  189-1,  Bd.  33,  S.  376. 

6  Krawkow  :   Ibid.,  1897,  Bd.  40,  S.  195. 


THE   CHEMISTRY  OF   THE  ANIMAL   BODY.  579 

Nucleo-proteids,  or  Nucleo-albumins '  and  Nucleic  Acids. — These  are  compounds 
of  proteid  with  nuclein,  which  latter  yields  phosphoric  acid  on  decomposition.  If  nucleo- 
proteid,  which  is  found  in  every  cell,  be  digested  with  pepsin-hydrochloric  acid,  there  remains 
a  residue  of  insoluble  nuclein,  which  is  likewise  insoluble  in  water  but  soluble  in  alkalies. 
If  this  nuclein  yields  xanthin  bases  on  further  decomposition,  it  is  called  true  nuclein;  if  it 
fails  to  yield  these  bases,  it  is  called  paranuclein  or  pseudonuclein.  Nucleo-proteids 
yielding  proteid  and  paranuclein  on  decomposition  include  the  casein  of  milk,  pyin  of 
the  pleural  cavity,  vitellin  of  the  egg,  Bunge's  iron-containing  hsematogen  of  the  egg, 
as  well  as  nucleo-proteids  found  in  all  protoplasm.  They  all  contain  iron.  Paranuclein 
is  probably  absorbable  (see  p.  514).  Casein  yields  on  peptic  digestion  phosphorized 
albumoses  from  which  paranuclein  is  split :  this  cleavage  is  followed  by  the  further 
digestion  of  the  albumose  and  the  gradual  solution  of  the  paranuclein.-'  Kobrak3  shows 
that  woman's  casein  has  two-thirds  the  acidity  of  cow's  casein,  but  that  the  former  dis- 
solved and  reprecipitated  six  times  has  the  same  properties  as  the  latter.  He  believes  that 
woman's  casein  may  consist  of  cow's  casein  united  with  another  product  of  more  basic 
properties. 

A  second  group  of  nucleo-proteids  yields  true  nuclein  on  decomposition.  This  true  nuclein 
is  a  modified  form  of  the  original  nucleo-proteid,  and  consists  of  nucleic  acid  in  combination 
with  proteid.  On  decomposition  the  nuclein  breaks  up  into  its  constituent  proteid  and  nucleic 
acid,  which  latter  always  yields  one  or  more  of  the  xanthin  bases,  which  arc.  therefore, 
called  nuclein  bases.  The  nucleic  acid  is  similar  to  that  derived  from  sperm,  which  is 
combined  with  protamin  in  the  sperm  nucleus.  The  nucleic  acid  of  yeast  nuclein  yields 
guanin  and  adenin,  that  of  a  bull's  testicle  adenin,  hypoxanthin,  and  xanthin,  that  of  the 
thymus  adenin  and  guanin,  that  of  the  pancreas  guanin  alone.  The  latter  has  been 
termed  "  guanylic  acid,"  and  "adenylic"  and  "xanthylic"  acids  may  also  be  considered 
individual  nucleic  acids.  Each  one  of  this  family  of  acids  has  the  power  of  combining 
with  any  soluble  proteid  to  form  nucleo-proteid,  hence  there  may  exist  a  large  variety 
of  nucleo-proteids.  And  the  variety  is  further  increased  by  the  diversity  of  other  decom- 
position products  yielded  by  the  various  nucleic  acids.  Thus  most  nucleic  acids  yield 
thymic  acid,  which,  however,  cannot  be  found  in  pancreas  nucleo-proteid.  A  crystalline 
base  called  cytosin  has  been  discovered  in  thymus  nucleic  acid.  Some  nucleic  acids,  like 
that  derived  from  yeast,  readily  yield  carbohydrates  (a  hexose  and  a  pentose) :  while  others, 
like  thymus  nucleic  acid,  show  the  presence  of  the  carbohydrate  group  only  in  the  pro- 
duction of  levulic  acid  after  very  thorough  decomposition  ;  and  still  others  (salmon  sperm) 
fail  to  indicate  the  presence  of  any  carbohydrate  radicle.  According  to  Kossel,  nuclei 
may  at  times  contain  free  nucleic  acid.  According  to  Bang,4  nucleic  acid  may  unite  in 
three   ways:  with  protamin,  as  in  sperm  nucleic  acid;  loosely  with  proteid,  as  in  most 

nucleo-proteids;  and  strongly  with  proteid,  as  in  pancreas  nucleo-proteid.     Thelast-nai 1 

pancreas  nucleic  acid  yields  guanin  on  decomposition,  and  has  been  termed  "guanylic 
arid."  Bang  gives  the  following  analysis :  guanin,  36  percent,  (containing  nine-tenths 
of  all  the  nitrogen  present);  a  little  ammonia;  a  pentose,  30  per  cent.,  and  I '_(),.  I7.»'. 
per  cent.     The  rest  unaccounted  for  is  17.5  per  cent. 

Phospho-glyco-proteids. — This  class  is  represented  by  Hammarsten's  hdico-proteid, 
which  yields  paranuclein.  and,  unlike  other  nucleo-proteids  of  the  paranuclein  class,  it 
yields  a  reducing  carbohydrate  on  boiling  with  acids. 

The  Albuminoids.  -These  are  bodies  derived  from  tine  proteid  in  the  body,  but  nol 
themselves  convertible  into  proteid.  They  are  resistant  to  the  ordinary  proteid  solvents, 
and  as  a  rule  exist  in  the  solid  state  when  in  the  body. 

1  These  two  terms  arc  used  here  as  synonymous,  though  Hammarsten  would  confine  the 
term  nucleo-albmnin  to  those  proteids  which  yield  paranuclein. 

2  Salkowski:  Zeitschrift fur  physiologische  <'li'ini<\  189!*,  I'll.  27,  8.  297. 
»  I'lirnjrrx  Archiv,   1900,  P.d.  80,  S.  69. 

*  Zeitschrift  fiir  physiohgisehe  Chemie,  1898,  Bd.  26,  S.  133. 


>n  AN    AMERICAN    TEXT- HOOK    OF   PHYSIOLOGY. 

Collagen. — This  is  the  chief  constituent  of  the  fibres  of  connective  tissue,  of  the 
organic  matter  of  bone  (ossein)  and  is  likewise  one  of  the  constituents  of  cartilage.  Col- 
lagen is  insoluble  in  water,  dilute  acids  and  alkalies.  On  boiling  with  water  it  forms 
gelatin  through  hydration,  which  is  soluble  in  hot  water,  but  gelatinizes  on  cooling  (as  in 
bouillon).  Dry  gelatin  .-wells  when  broughl  into  cold  water.  By  continuous  boiling  or  by 
gastric  or  tryptic  digestion  further  hydration  takes  place  with  the  formation  of  soluble 
gelatin  peptone.  Gelatin  fed  will  not  take  the  place  of  proteid,  but.  like  sugar,  only  more 
effectively,  it  may  prevent  proteid  waste  by  being  burned  in  its  stead.1  Gelatin  .yields  leucin 
and  glycocoll  on  decomposition,  but  no  tyrosin.  It  therefore  gives  the  biuret  reaction,  but 
none  with  Millon's  reagent.  It  contains  but  little  sulphur.  It  yields  about  the  same 
ainido-  acids  as  ordinary  proteid. 

Elastin. — This  is  very  insoluble  in  almost  all  reagents  and  in  boiling  water.  On 
decomposition  it  yields  leucin,  tyrosin,  glycocoll,  and  lysatin.  It  is  slowly  hydratcd  by 
boiling  with  dilute  acids,  and  by  pepsin  hydrochloric  acid.  It  contains  very  little  sulphur, 
and  gives  Millon's  test.  It  is  found  in  various  connective  tissues,  and  especially  in  the 
cervical  ligament. 

Keratin  and  Neuro-keratin. — These  are  insoluble  in  water,  dilute  acids  and  alkalies; 
insoluble  in  pepsin  hydrochloric  acid,  and  alkaline  solutions  of  trypsin.  Keratin  is  found 
in  all  horny  structures,  in  epidermis,  hair,  wool,  nails,  hoofs,  horn,  feathers,  tortoise-shell, 
whalebone,  etc.  Neuro-keratin  has  been  discovered  in  the  brain,  and  in  the  medullary 
sheath  of  nerve-fibres.2  On  decomposition  with  hydrochloric  acid  keratin  yields  all  the 
products  given  by  simple  proteids.  It  contains  more  sulphur  than  simple  proteid  and 
yields  more  tyrosin.  Drechsel3  believes  that  it  is  transformed  from  simple  proteid  by  the 
substitution  of  sulphur  for  some  of  the  oxygen  and  of  tyrosin  for  leucin  or  other  amido- 
acid.  Part  of  the  sulphur  is  loosely  combined,  and  a  lead  comb  turns  hair  black,  due  to 
the  formation  of  lead  sulphide.  There  are  different  keratins,  and  their  sulphur  content 
varies  greatly. 

Histon. — Iliston  is  a  proteid  split  off  from  yeast  nuclein  and  the  nuclein  of  the  white 
blood-corpuscles  and  blood  plates.  Kossel  has  suggested  that  it  is  a  combination  of  pro- 
teid  and  protamin,  which  the  investigations  of  Bang  *  tend  to  confirm. 

Protamins  and  Remarks  on  the  Theoretical  Composition  of  the 
Proteid  Molecule. — The  protamins  have  been  discovered  in  fish-sperm 
united  with  nucleic  acid.  According  to  Kossel,  protamins  are  the  simplest 
proteids.  They  till  give  the  biuret  test.  On  heating  with  dilute  acid  or  in 
tryptic  digestion  they  are  converted  into  protone  (protamin  peptone),  and 
then  they  break  up  into  amido  acids.  Several  protamins  have  been  dis- 
covered. That  obtained  from  sturgeon-sperm  is  called  sturin,  from  the 
herring,  clupein,  from  the  salmon,  salmin,  and  from  the  mackerel,  scombrin. 
Sturin,  according  to  Kossel,5  breaks  up  as  follows  ; 

C36Hfi9N1907  +  5H20  =  C6H9N302  +  3C6HMN402  +  C6H14N202 

sturin.  Ilistidin.  Axginin.  I.ysin. 

Kossel'-  investigations  show  thai  salmin  and  clupein  are  identical  and 
yield  on  decomposition  arginin  and  amido  valerianic  acid,  while  scombrin 
also  yields  arginin,  without  any  histidin  or  lvsin.6 

1  Voit :  Zeitnehrififui  Biolopie,  1872,  Bd.  8,  S.  297. 

1  Kulme  and  Chittenden:    Ibid.,  1890,  Bd.  26,  S.  291. 

3   Ladenbuipfs   Il<atihiijr/>rlnirlt  <hr  (  'hrmir,  lSS.j,   Bd.  3   S.  571. 

*  ZeiUchrift  fw  phyaiologuche  Chemie,  1899,  Bd.  27,  S.  463. 

5  Deutsche  medicini8che  Wochensehrift,  1898,  No.  37. 

6  Zeitschrifi  fiir  physiologischc  Chemie,  1899   Bd.  26,  S.  588. 


THE   CHEMISTRY  OF   Till-:  ANIMAL   BODY.  581 

All  proteids  yield  histidin,  arginin,  and  lvsin  on  decomposition.  As 
regards  the  composition  of  the  proteid  molecule,  Kossel  pictures  a  protamin 
nucleus  like  sturin,  to  which  may  be  attached  leucin,  tyrosin,  glucosamin,  or 
glycocoll,  and  to  these  again  sulphur,  iodine,  or  iron.  Treatment  of  proteid 
with  20  per  cent,  hydrochloric  acid  or  tryptic  digestion  may  break  it  up  into 
leucin,  tyrosin,  histidin,  argenin,  lvsin,  etc.  Kossel  speaks  of  histidin,  arginin, 
and  lysin  as  hexon-bases,  since  they  (and  leucin  also)  contain  six  atoms  of 
carbon,  and  he  calls  attention  to  the  fact  that  in  this  respect  they  are  similar 
to  the  carboydrates.  Just  as  carbohydrates  exist  as  poly-hexoscs,  so  prota- 
mins  and  proteids  may  be  built  up  as  poly-hcxon-bases.  Cohn  has  found 
that  proteid  may  yield  as  much  as  50  per  cent,  of  leucin. 

The  products  derived  from  proteid  in  metabolism  are  different  from  the 
above.  Thus  it  has  been  found  that  the  body's  proteid,  the  proteid  from 
meat,  and  gelatin,  may  all  yield  about  60  per  cent,  of  dextrose  in  diabetes.1 
It  has  been  further  shown  2  that  the  metabolism  of  the  body's  proteid,  of 
casein,  and  of  gelatin  yields  between  3  and  4  per  cent,  of  glycocoll,  which 
may  be  eliminated  as  hippuric  acid.  It  is  possible  to  conceive  of  a  carbo- 
hydrate portion  united  to  a  protamin  nucleus  and  to  amido  bodies  such  as 
glycocoll 3  (see  p.  558). 

Miiller  and  Socman 4  have  declared  that  the  source  of  the  sugar  in 
diabetes  must  be  the  hexon-bases  and  leucin,  but  Halsey5  has  shown  that 
feeding  leucin  will  not  increase  the  sugar  in  diabetes.  Halsey  suggests  a 
synthetic  formation  of  sugar  from  lower  proteid  decomposition-products,  but 
a  synthetic  formation  of  sugar  in  the  animal  has  never  been  shown.  It  must 
be  admitted  that  we  are  still  in  the  dark  regarding  even  the  simplest  expres- 
sion of  the  constitution  of  proteid. 

It  has  been  impossible  within  the  limits  set  to  do  more  than  to  glance  at 
the  proteid  bodies.  Many  facts  concerning  the  behavior  of  proteids  have 
been  mentioned  throughout  the  text,  and  cannot  be  classified  here. 

The  size  of  the  proteid  molecule  must  be  very  great,  and  one  computation 
shows  the  following  figures6  (see  also  p.  577) : 

C204H322N.r)2O66S2.  CV26H1I71Ni940214S3. 

Egg-albumin.  Proteid  from  haemoglobin  (dog). 

It  is  well,  perhaps,  finally,  to  speak  of  experiments  which,  however  incom- 
plete, at  least  throw  some  light  on  the  possibilities  of  the  problem  of  the  syn- 
thesis of  proteid.     Lilienfeld7  through  the  condensation  of  the  ethyl-ester  of 

1  Keilly,  Nolan,  and  Lusk :  American  Journal  of  Physiology,  1898,  vol.  i.  p.  395. 

2  Parker  and  Lusk  :    I  hid.,  L900,  vol.  iii.  J>.  -J7-J. 

3  Ray,  McDermott,  and  Lusk  :   Ibid,,  1S99,  vol.  iii.  p,  153. 
*  Deutsche  medicinisehe  Wochenschrift,  1899,  S.  209. 

5  Sitzungsberichte  der  Gesellschaft  zur  Befordeiimg  der  gesammten  NaturvnssenwhafienjMU  Marburg, 
1899,  S.  L02. 

6  Bnnge  :   Physiologische  Chemie,  3d  ed.,  1893,  S.  56. 

7  Verhandlungen  der  Berliner  physiologischen  Gesellseliaft,  Archiv  fur  Physiologic,  1894, 
S.  383. 


582  AN    AMERICAN    TEXT-BOOK    OF   PHYSIOLOGY. 

glyoocoll  has  obtained  a  body  insoluble  in  water,  but  swelling  in  it,  forming  a 
gelatinous  mass.  The  substance  gives  the  biuret  reaction,  is  insoluble  in 
alcohol  and  dilute  hydrochloric  acid,  but  dissolves  in  pepsin-hydrochloric 
acid.  These  reactions  show  its  kinship  to  gelatin.  Lilienfeld  likewise  de- 
scribes a  synthetically  formed  peptone  and  a  coagulable  proteid,1  the  peptone 
formed  principally  through  condensation  of  the  above-described  product  with 
the  ethyl-esters  of  the  amido-  bodies,  leucin  and  ty  rosin,  the  proteid  from  the 
same  with  addition  of  formic  aldehyde.  Grimaux  likewise  has  produced, 
with  other  reagents,  colloids  which  resemble  proteids.  Probably  none  of 
these  substances  are  native  proteids,  but  they  furnish  indications  of  lines  of 
attack  for  the  future  mastery  which  in  time  is  sure. 

1  Verhandlungen  der  Berliner  physiologischen  Gesellschaft,  Archiv  fur  Physiologie,  1894, 
S.  555. 


INDEX 


Abdominal  muscles,   action   of,  in  vomiting, 
387 
respiratory  action  of,  407 

respiration,  definition  of,  398 
Absorbents,  318 
Absorption,  effect  of  alcohol  on,  535 

in  the  small  intestine,  313 

in  the  stomach,  312 

mechanism  of,  312 

nature  of  process,  27 

of  fats,  317 

of  gases  by  liquids,  414 

of  proteids,  316 

of  sugars,  317 

of  water  and  salts,  318 

part  played  by  leucocytes  in,  48 

paths  of,  311 

spectrum  of  oxyhemoglobin,  41 
Accelerator  centre,  cardiac,  177 
respiratory,  457 

nerves  of  the  heart,  167,  168,  169 
Accessory  articles  of  the  diet,  357 

thyroids,  268 
Acetic  acid,  536 

Acetone,  relation  of,  to  fat  metabolism,  539 
Acetonitril,  542 
Acetonuria,  537 
Acetyl-acetic  acid,  537 
Acetyl-propionic  acid,  538 
Achroodextrin.  285,  566 
Acid,  acetic,  536 

acetyl-acetic,  537 

acetyl-propionic,  538 

amido-acetic,  537 

amido-ethyl-sulphonic,  543 

a-amido-a-thiopropionic,  546 

aspartic,  557 

benzoic,  569 

butyric,  539 

capric,  541 

caproic,  540 

caprylic,  541 

carbamic,  548 

carbolic,  569 

carbonic,  chemical  structure  of,  545 

choleic,  543 

cholic,  543 

chondroitic,  578 

cynurenic,  571 

diamido-acetic,  551 

o-e-diamido-caproic,  552 

diamido- valeric,  ~>.->2 

dithio-diamido-ethidene  lactic,  547 

fellic,  543 

formic,  534 

glutamic,  558 

glycerin  phosphoric,  559 

glycuronic,  567 

hippuric,  33ft,  569 

homogentisic,  570 

hydriodic,  509 

hydrobromic,  509 

hydrochloric,  507 

hydrocumaric,  570 


Acid,  hydrocyanic,  542 

hydrofluoric,  510 

iso-butyl  amido-acetic,  540 

iso-valerianic,  539 

lactic,  545 

levulic,  538 

malic,  558 

mercapturic,  547 

metapliosphoric,  514 

methyl  amido-acetic,  538 

monobasic  fatty,  532 

nucleic,  579 

oleic,  560 

orthophosphoric,  514 

oxalic,  557 

oxaluric,  555 

oxybutyric,  548 

oxyphenyl-acetic,  570 

oxy  phenyl -am  ido-propionic,  570 

palmitic,  541 

parabanic,  555 

phenaceturic,  569 

phenyl-acetic,  569 

propionic,  538 

sarco-lactic,  546 

silicic,  519 

stearic,  541 

succinic,  557 

sulphuric,  506 

sulphurous,  506 

thiolactic,  547 

thvmic,  579 

uric,  322,  338,  554,  557 
Acids,  effect  of,  on  pancreas,  236 
Acinus,  definition  of,  212 
Acromegaly,  273 

Adamkiewicz  reaction  for  proteids,  576 
Addison's  disease,  '.'71 
Adenin,  :i:«»,  554 
Adipocere,  541,  560 

Adrenal  bodies,   internal  secretion  of,  27'.' 

removal  of,  271 

secretory  nerves  of.  272 
Adrenal  extracts,  physiological  action  of.  271 

Afferent  respiratory  nerves,  460 

Age,  influence  of.  on  heal  production,  182 

on  pulse  rate,  121 

on  respiration.   125 
relation  of  body  temperature  to.  469 
Air,  alveolar,  composition  of,  113 
atmospheric,  composition  of,  110,  113 
complemental,  \'~. 

expired,   COmpOSil  Ion   of.    I  |0 

inspired,  composil ion  of,  l lo 

in  t  lie  lungs,   renewal  of,    1 13 

passages,  obsl  i  ucl  ion  of,  152 
residual.   127 

respiratory  changes  In,  110 
stationary,  127 
suction  of,  into  veins,  97 
supplemental,  127 
tidal,  volume  of,  126 
variations  in  the  composition  of,  435 
Albuminates,  577 

583 


584 


INDEX. 


Albuminoids,  digestion  of,  in  the  stomach.  297 

enumeration  of,  577 

nutritive  value  of,  "-'77,  349 

properties  of,  579 

protection  of  proteids  by,  '■'>l'.< 

tryptic  digestion  of,  304 
Albuminous  glands,  216 
Albumins,  properties  of,  577 
Albumose  injections,  effect   of,  on  blood,  coagu- 

lation,  62 
Alcaptonuria,  570 
Alcohol,  absorption  of,  in  the  stomach,  313 

amy  I.  539 

cerotyl,  540 

cetyl,  540 

ethyl.  535 

melicyl,  540 

nutritive  value  of,  358 

physiological  action  of,  357,  535 

propyl.  536,  538 

toxic  effects  of,  359 
Alcoholic  fermentation,  535 
Alcohols,  monatomic,  531 
Aldehydes,  general  properties  of,  534 
Aldoso.  561 
Alimentary  canal,  movements  of,  369 

principles,  276 
Allantoic,  555 

Alloxunc  bases,  338,  339,  552 
Altitude,  effect   of,  on   the  number  of  red  cor- 
puscles, 46 
Alveolar  air,  composition  of,  413 

capacity,  427 

tension  of  carbon-dioxide,  413 
of  oxygen,  413 
Alveolus,  glandular,  definition  of,  212 
Amido-acetic  acid,  537 
Amido-acids,  properties  of,  538 
Amines,  definition  of,  541 
Ammonia,  inhalation  of,  440 

occurrence  of,  511 

origin  of,  in  the  body,  511 

properties  of,  511 
Ammoniacal  fermentation  of  urine,  512 
Ammonium  carbamate,  548 

carbonate,  523 

cyanate,  542 

magnesium  phosphate,  527 
Amniotic  fluid,  inhibitory  eflect  of,  on  respira- 
tion, 464 
Amoeboid  movement  of  leucocytes,  48 
Ampho-peptone,  definition  of,  293 
Ainygdalin,  fermentative  decomposition  of,  542 
Amy]  alcohol,  539 
Amylodezl  rin,  566 
Amyloid,  578 

Amylolytic  enzyme  of  gastric  juice  in  the  dog, 
296 
of  succns  entei  icns,  308 
of  the  liver,  330 

enzymes,  definition  of,  280 
action  of.  in    I  lie  bod  v,  2*5 
Amylopsin,  232,  280 

action  of,  on  starch.  566 

digestive  action  of,  305 

■  mi  in  rence  of,  304 

properties  of,  305 
Anabolism,  definition  of,  19 
A  usesthetics,  effect  of,  on  body-temperature,  472 
Animal  foods,  composition  of,  278 

heat,   167 
source  of,  17  1 
Annulus  Vieussens,  L59 
Antalbumid,  293 
Antilytic  secretion,  230 
Antimony  poisoning,  5]  I 
Anti-peptone,  definition  <>f,  293 


Anti-peptone,  nature  of,  302 
Antiperistalsis,  intestinal,  383 
of  the  stomach,  379 

Antrum  pylori,  377 
Apex  beat,  117 

preparation  of  the  frog's  heart,  188 

ventricular,  rhythmicity  of,  151 
Apncea,  definition  of,  440 

foetal,  164 

phenomena  of,  441 

relation  of  vagi  to,  442 
Apomorphia,  action  of,  389 
Arabinose,  562 
Arginin,  552 
Argon  of  the  blood,  417 
Aromatic  compounds  m  urine,  572 

metabolism  of,  568,  569 
Arsenic  poisoning,  514 
Arterial  blood-pressure,  explanation  of,  92 

pulse,  cause  of,  93 
definition,  139 
extinction  of,  94 
Arteries,  coronary,  179 

elongation  of,  14(1 

rate  of  flow  in,  101 
Artificial  respiration,  circulatory   effects  of,  453 

methods  of  maintaining,  446 
Asparagin,  558 
Aspartic  acid,  557 
Asphyxia,  441 

circulatory  changes  in,  445 

efl'ects  of,  on  the  blood-vessels,  202 
on  the  respiratory  rhythm,  425 

stages  of,  445 
Aspiration  of  the  thorax,  influence  of,  on  the 
circulation,  77,  95 
on  the  lymph-flow,  147 
on  venous  circulation,  77,  95 
Assimilation,  general  characteristics  of,  19 
Associated  respiratory  movements,  408 
Asymmetrical  carbon  atom,  definition  of,  545 
Atelectasis,  396 

Atmospheric  air,  composition  of,  410,  413 
Atrophv  of  the  heart  after  section  of  the  vagi, 

167 
Atropin,  action  of,  on  salivary  glands,  222,  229 
on  sweat  glands,  260 

eflect  of,  on  body-temperature,  472 
Augmentor  centre  of  the  heart,  177 

nerves  of  the  heart,  161,  lt>7 
Auricles,  connection  of,  135 

degree  of  emptying,  in  systole,  138 

functions  of,  135 

influence  of,  on  venous  blood-flow,  136 

negative  pressure  in  the,  137,  138 

systolic  changes  in  the,  115 
Auricular  pressure,  135,  137 

systole,  duration  of,  124,  136 

eflect  of,  on  venous  blood-flow,  138 
on  ventricular  tilling,  137 
Auriculo-ventricular  valves,  108 
Auscultation,  118 
Axilla,  temperature  in  the,  468 

Bacterial    decomposition   in    the    intestines, 

309 
Banting  diet.  :i.">:: 
Barometric  pressures,  effect  of,  on  respiration, 

434 
Bartholin,  duct  of,  '.'17 
Basophiles,  47 

Baths,  influence  of,  on   body-temperature,  471 
Beckmann's  apparatus,  68 
Beef-tea,  physiological  action  of,  359 
I  leer.  535 
Beeswax,  540 
Benzoic  acid.  340,  569 


INDEX. 


585 


Benzol,  molecular  constitution  of,  568 
Beuzopyrol,  571 
Bidder's  ganglion,  148 
Bile,  amount  secreted,  246,  321 
antiseptic  property  of,  326 
composition  of,  245,  321 

discharge  of,  from  the  gall-bladder,  248,  249 
fatty  acids  of  the,  541 

influence  of,  on  ein unification  of  fats,  307 
mineral,  constituents  of,  530 
pigments  of,  245,  322 
physiological  value  of,  325 
relation  of,  to  fat  absorption,  325 
secretion  of,  246 
sulphur  of,  507 
Bile-acids.  245 

detection  of,  324 
Neukomm's  test  for,  545 
occurrence  of,  323 
origin  of,  324 

Pettenkofer's  test  for,  324,  544 
relation  of,  to  fat  absorption,  326 
Bile-capillaries,  244 
Bile-ducts,  occlusion  of,  249 
Bile-pigments,  322 

chemical  properties  of,  574 
Gmelin's  test  for,  322,  574 
origin  of,  45,  530 
Bile-salts,  245 

chemistry  of,  543 
circulation  of,  544 
Bile-secretion,  normal  mechanism  of,  248 

relation  of,  to  blood-flow  in  the  liver,  247 
Bile-vessels,  motor  nerves  of,  248 
Biliary  fistula;,  321 
Bilievanin,  574 
Bilirubin,  245,  574 
Biliverdin,  245,  574 
Bilixanthin,  574 
Biuret,  549 
Bladder,  urinary,  movements  of,  369,  390 

vaso-motor  nerves  of,  209 
Blood,  33 

chemical  composition  of,  50 
circulation  of,  76 
coagulation  of,  54 
defibrinated,  34 
distribution  of,  in  tbe  body,  63 
foreign,  action  of,  on  tbe  heart,  192 
gaseous  exchanges  of  the,  411 
general  function  of  the,  33 
histological  structure  of,  33 
identification  of,  573 
oxidations  in  the,  423 
reaction  of  tbe,  34,  290 
regeneration  of,  after  hemorrhage,  63 
specific  gravity  of,  31 
total  quantity  of,  in  the  body,  63 
transfusion,  64 
Blood-corpuscles,  inorganic  salts  of,  50,  530 

varieties  of,  33 
Blood-gases,  analyses  of,  411 
extraction  of,  420 
tension  of,  415 
Blood-leucocytes,  47 
Blood-plasma,  color  of,  33 
composition  of,  51 
inorganic  salts  of,  50 
Blood-plates,  49 
Blood -pressure,  aortic,  91 
capillary,  84,  93 

effect  of  the  accelerator  nerves  on,  170 
effect  of  the  depressor  nerve  on,  173 
effect  of,  on  renal  secret  ion,  253,  256 
mean,  definition  of,  90 
methods  of  measuring,  84,  85 
origin  of  the,  91,92 


Blood-pressure,  pulmonary,  91 

respiratory  changes  in,  147 

venous,  91,  94 
Blood-serum,  composition  of,  51 

definition,  34 

mineral  constituents  of,  530 

osmotic  pressure  of,  68 
Bodily  metabolism,  estimation  of,  343 
movements,  effect  of,  on  lymph-flow,  147 
temperature,    effect    of,   on    respiratory    ex- 
changes, 432 
Body-weight,  influence  of,  on  heat-production, 
482 

loss  of,  from  starvation,  362 
Border-cells  of  the  gastric  glands,  237,  238 
Brain,  vaso-motor  nerves  of  the,  203 
Bromelin,  280 
Bromine,  508 
Bronchial  capacity,  427 
Broncho-constrictor  nerves,  465 
Broncho-dilator  nerves,  465 
Brunner's  glands,  243 
Butfy  coat,  55 
Butyric  acid,  539 

Cadaverin.  543 
Caffein,  553 

action  of,  on  the  kidneys,  254 
on  body-temperature,  472 
Calcium,  absorption  of,  525 
excretion  of,  526 
physiological  value  of,  524 
relation  of,  to  heart  muscle,  151 
carbonates,  524 
chloride,  523 
fluoride,  510,  523 
phosphates,  523    ■ 
salts,  action  of,  on  the  heart,  190 
amount  of,  in  fibrin,  58 
excretion  of,  356 
nutritive  value  of,  356 
relation  of,  to  blood-coagulation,  57,  524 
sulphate,  523 
Calorie,  definition  of.  504 
Calorimetric  equivalent,  478 
Calorimetry,    direct     and    indirect,    365,    475, 

478 
Cane  sugar,  injection  of,  317 

inversion  of,  565 
Capacity  of  the  heart -ventricles,  105 
Capillaries,  biliary,  244 
blood,  length  of,  79 
permeability  of,  TO 
pressure  in  the.  -  1 
rate  of  flow  in.  101 
resistance  in  the,  SI 
structure  of.  B0 

time,  spent  by  the  blood  in,  103 
secretion  of  the  fundic  viands,  238 
Capillary  circulation,  microscopic  characters  of, 
*80 
pressure,  origin  of,  93 
relation  of,  to  lymph  formation,  72,  75 
Capric  acid.  ">  1 1 
Caproic  acid,  540 
( 'aprylic  acid,  511 

Capsules,  suprarenal,  extirpation  of,  '.'71 
<  larbamic  acid.  5  18 

i  elal  ion  of,  to  u  rea  formal  ion,  336 
( larbamide,  5 18 

Carbo-bsamoglobin,  nature  of,  39 
Carbohydrates,  absorption  of,  317 
affinity  of  ceil  substance  for,  568 
chemist  ry  of,  561 
combu6< ion  equivalent  of,  365 
ill  tin  it  ion  of,  "'lil 

digestion  of,  in  the  stomach, 296 


586 


IXDEX. 


Carbohydrates,  dynamic  value  of,  475 
fermentation  of,  in  the  intestines,  310 
molecular  constitution  of,  561 
nutritive  value  of,  277,  353 
origin  of  fat  from,  35:2 
proteid-protection  by,  568 
synthesis  of,  26 
Carbon,  metabolism  of,  518 
occurrence  of,  516 
properties  of,  516 
Carbon -dioxide,  action  of,  on  the  heart,  191 
dyspnoea,  444 

elimination,  conditions  affecting,  429 
cutaneous,  422 
estimation  of,  428 
inhalation,  effects  of,  440 
occurrence  of,  517 
of  the  blood,  extraction  of,  517 
properties  of,  518 
tension  of,  in  the  alveoli,  413 
in  the  blood,  416 
Carbon  equilibrium,  definition  of,  345 
Carbonic  acid,  chemical  constitution  of,  545 
Carbon    monoxide,    absorption      spectrum     of, 
44 
composition  of,  38 
properties  of,  517 
Carbon-monoxide  lnemoglobiu,  517 

inhalation,  440 
Carburetted  hydrogen  inhalation,  440 
Cardiac  centre,  augmentor,  177 
inhibitory,  176 
cycle,  analysis  of,  122 
definition  of,  104 
duration  of,  123 
dyspnoea,  444 

excitation,  propagation  of,-during  vagus  stim- 
ulation, 163 
impulse,  117 
nerves,  anatomy  of,  159 
classification  of,  171 
extrinsic,  159 
of  liogs,  160 
of  mammals,  160 
Cardio  inhibitory  centre,  respiratory  variations 

in,  451 
Cardio  pneumatic  movements,  412 
Cardiogram,  117 
Cardiometer,  106 
Cam  in,  554 
Casein,  "Jfil 

composition  of,  579 
curd  ling  of,  by  acids,  296 
by  rennin,  295 
Catalysis,  282,  503 
Cell-differentiation,  22 
Cell-division,  20 

Cell-granules  of  glandular  epithelium,  216 
Cellulose,  565 

Centre,  augmentor  of  the  heart,  177 
cardio-  inhibitory,  176 
defecation,  387 
d(  glutition,  377 
expiratory,  l.">7 
inspiratory,  157 
micturition,  391,  393 
pei  ipberal  reflex,  178 
respiratoi  y,  455 
salivary  secretory,  230 
sweat,  '-'(in 
thermogenic,  491 
vaso-motor,  198 
vomiting,  389 
<  en tri petal  nerves  of  the  heart,  171 
( lentrosome,  22 
Cerebral  circulation,  203 
crossed,  443 


Cerebral  cortex,  relation  of,  to  the  vaso-motor 

centre,-  202 
Cerebri n,  559 
Cerotyl  alcohol,  540 
Cerumen,  L'57 
Cervical  sympathetic,  vaso-motor  function  of, 

193 
Cetyl  alcohol,  540 
Chest,  effects  of  opening  the,  115 
Cheyne-Stokes  respiration,  424 
( Ihief  cells  of  the  gastric  glands,  237 
( Ihinese  wax,  540 
Chinolin,  571 

Chloral,   effect  of,  on  the   respiratory  rhythm, 
425 

hydrate,  536 
Chlorine,  inhalation  of,  440 

occurrence  of,  507 
Chlorocruorin,  578 
Chloroform,  fate  of,  in  the  body,  533 
Chocolate,  nutritive  value  of,  357 
Cholagogues,  246 
Cholesterin,  575 

amount  of,  in  the  blood,  51 

distribution  of,  325 

excretion  of,  325 

of  the  bile,  245 

of  milk,  261 

of  sebaceous  secretion,  257 
Choletelin,  574 
Cholin,  541,  543 
ChoJo-haematin,  323 
Chondroitic  acid,  578 
Chondro-mucoid,  578 

Chorda  tympani  nerve,  vaso-dilator  function  of, 
i<i4 

Chordae  tendiueae,  109 
Chromatin,  22,  28 
Chromo-proteids,  576 
Chromosomes,  22,  28 
Chyme,  287,  381 

Circulating  proteid,  definition  of,  346 
Circulation,  capillary,  velocity  of,  83 
cerebral,  203 
of  hydriodic  acid,  509 
of  hvdrofluoric  acid,  510 
of  the  bile,  323,  324 
of  the  blood,  causes  of,  77 
definition,  76 
discovery  of,  76 
microscopic  appearances  of,  80 
portal,  77 

puhuonarv,  78,  103 
rate  of,  79,  98 
pulmonary,  103 
renal,  255 
Circulation-time,  79 

Climate,  influence  of,  on  body-temperature,  469 
Clothing,  influence  of,  on  heat-loss,  486 
Clotting  of  the  blood,  55 

of  milk,  295 
( 'lupein,  580 

COa  elimination,  cutaneous,  258,  342 
during  muscular  work,  361 
sleep,  361 
Coagulated  proteids,  properties  of,  578 
Coagulating  enzymes,  definition  of,  280 
Coagulation   of   the  blood,    accelerating  agents 
of  the,  <ii 
conditions  necessary  for,  57 
description  of  the.  51 
nature  of,  60 
intravascular,  60 

retarding  influences  affecting,  61,  62 
theories  of  the,  55,  56 
time  taken  by  the,  55 
uses  of,  55 


INDEX. 


587 


Coagulation  of  milk,  295 

Cocaine,  effect  of,  on  intestinal  movements,  384 

Coefficient  of   absorption  of  liquids  for  gases. 

414 
Coffee,  nutritive  value  of,  357 
Cold,  effect  of,  on  coagulation  of  the  blood,  61 
Collagen,  580 
Colloid,  578 

substance  of  the  thyroid,  secretion  of,  268 
Colostrum  corpuscles,  origin  of,  263 

definition  of,  264 
Combined  proteids,  579 
Combustion,  501 

equivalent  of  foods,  365 
Comedones,  257 
Complemental  air,  427 
Compressed  air,  respiration  of,  452 
Condiments,  nutritive  value  of,  359 
Conductivity  of  living  matter,  21 
Conduction    in    the   heart  of    the   contraction 

wave,  154 
Congo-red  test  for  mineral  acids,  289 
Conjugated  sulphates,  nutritive  history  of,  340 
Consciousness,  29 
Contractility  of  living  matter,  21 

of  plain  muscle,  370 
Contraction  volume  of  the  heart,  105 

wave  of  the  heart,  rate  of  propagation  of,  153 
Coronary  arteries,  anatomy  of,  179,  180 
ligation  of,  181,  183 

circulation,  effect  of  ventricular  systole  on, 
185 
volume  of,  184 

veins,  closure  of,  184 
Corpora  Arantii,  112 
Corpuscles,  colostrum,  263 

of  the  blood,  45 

salivary,  283 
Cortex  cerebri,  connection  of,  with  the  respira- 
tory centre,  463 
Cortical  stimulation,  vascular  effects  of,  202 
Costal  respiration,  definition  of,  398 
Coughing,  454 
Coughs,  sympathetic,  455 
Crab-extract,  lymphagogic  action  of,  73 
Creatin,  chemical  constitution  of,  550 

nutritive  history  of,  339,  551 
Creatinin,  551 

nutritive  history  of,  339 
Cresol,  569 

elimination,  340 
Crossed  cerebral  circulation,  443 
Crying,  454 

Crystalloids,  diffusion  of,  69 
Crystals  of  CO-haemoglobin,  40 

of  hsemin,  44,  573 

of  haemoglobin,  39 
Cutaneous   nerves,  influence  of,  on  respiration, 
463 

respiraf  ion,  422 

secretion.  257 
Cyanamide,  542 
( 'yanogen  gas,  541 

inhalation.  440 
Cynurenic  acid,  571 
Cysteiu,  546 
Cystin,  547 

Cytology,  definition  of,  31 
Cytosin,  579 

"  Dangerous  region,"  97 

Decomposition,  bacterial,  in  the  intestines,  309 

Defecation,  386 

Defibrinated  blood,  definition  of,  34 

preparation  of,  55 
Deglutition,  372 
analysis  of,  376 


Deglutition,  apncea,  442 

centre  for,  .'J77 

explanation  of,  :;?r> 

nervous  regulation  of,  376 
Demilune.-,  219 
Depressor  nerve,  17.',  203 
Deutero-proteose,  definition  of,  293 
Dextrose,  action  of,  on   the  heart,  191 

amount  of,  in  the  blood,  51,  317 

origin  of,  563 

oxidation  of,  in  the  tissues,  317 

storage  of,  563 
Diabetes  mellitus,  dextrose  excreted  in,  354,  563 
fatty  acids  in,  536 
on  proteid  diet,  329 
phosphorus  excretion  in,  515 
relation  of  the  pancreas  to,  266 
Dialysis,  definition  of,  65 

of  soluble  substances,  69 
Diaphoretics,  effect  of,  on  heat  dissipation,  489 
Diaphragm,  movements  of,  398 
Diastase,  280 

Diastatic  enzymes,  280,  566 
Dicrotic  pulse,  144 

wave  of  the  pulse-curve,  143 
Diet,  accessory  articles  of,  357 

average,  for  man,  366 
Dietetics,  366 

Differential  manometer,  131 
Diffusion,  definition  of,  65 

of  proteids,  70 

through  membranes,  66 
Digastric  muscle,  372 
Digestion,  action  of  alcohol  on,  535 

gastric,  287 

in  the  large  intestine,  309 

influence  of,  on  respiratory  exchanges,  431 

intestinal,  299 

of  fats,  305 

of  proteids,  292,  301 

of  starch,  284 

pancreatic,  301,  308 

purpose  of,  275 

salivary,  283 
Digitalis,  effect  of,  on  the  respiratory  rhythm. 

425 
Dioxyacetone,  558 
Dioxyphenyl-acetic  acid,  570 
Disaccharides,  564 

digestion  of.  308 
Disassimilation,  definition  of,  19 

Dissociation  of  elect  inly  tes,  67 
Diuretics,  action  of,  25  I 
Drinking-water,  504 
Dropsy,  147 
Drowning,  phenomena  of,  445 

resuscitation  from,  445 
Drugs,  action  of.  on  body-temperature,  472 
on  salivary  glands,  '-''J','.  229 
on  sweat-glands,  260 
on  t  hei  mogenesis,  184 
on  thermolysis,  i-'1 
Duct  of  Bartholin,  217 

of  Ki vinos,  -.'17 

of  S  ten  son,  217 

of  Wharton,  217 

of  Wirsung,  231 
Dyslysin,  54  l 
Dyspepsia,  cause  of.  309 
Dyspnoea,  definil  ion  of.  1 1 1 

effect  of,  on  intestinal  movements,  386 

phenomena  of.  1 1 1 

variel  ies  of,  1 13,  1 1 1 

Eck  fistula.  :;::ii 

Edestine,  .".77 

Efferent  respiratory  nerves,  463 


588 


INDEX. 


Egg  albumin,  absorption  of,  315 
Elastin,  580 

Ele<  trical  changes  in  active  glands,  231 
in  the  beating  heart,  152,  153 
in  the  lnart,  during  vagus  stimulation,  164 
Electrolytes,  definition  of,  67 
Emigration  of  leucocytes,  83 
Emphysema,   influence   of,  on    tlie   respiratory 

rhythm,  424 
Emulsification  of  fats,  306 

influence  of  the  bile  on,  307 
Emulsions,  preparation  of,  307,  559 
Endocardiac   pressure   (see  Intracardiac  press- 
ure). 
Eocmata,  nutritive,  315 
Energy,  potential,  of  foods,  364 
Enzyme  action,  theories  of,  282 

glycolytic,  354 
Enzymes,  classification  of,  280 

composition  of,  279 

definition  of,  279 

effect  of,  on  blood  coagulation,  63 

general  properties  of,  281 

mode  of  action  of,  282 

of  pancreatic  juice,  332,  235,  301 

solubility  of,  281 
Eosinophiles,  47 
Epiguanin,  554 
Epinephrin,  272,  572 
Episarcin,  554 

"  Erection  "  of  the  heart,  114 
Erectores  spiuae  muscles,  respiratory  action  of, 

405 
Erytbroblasts,  15 
Erythrodextrin,  285,  566 
Erythrose,  562 

Escape  of  the  heart  from  vagus  inhibition,  163 
Ether,  ethyl.  536 
Ethereal  sulphates,  506 

of  the  urine,  572 
Ethers,  properties  of,  536 
Ethyl  alcohol,  535 
Ethylamine,  541 
Eudiometer,  421 
Eupnoea,  definition  of,  440 

Excitation,  cardiac,  electrical  variation  in,  153 
propagation  of,  153,  154 

wave,  cardiac,  152 
Excretiu,  occurrence  of,  in  feces,  320 
Excretions,  definition  of,  213 
Exercise,  effect  of  on  metabolism,  359 

on  pulserate,  121 
Expiration,  forced,  muscles  of,  407 

movements  of,  106 
Expiratory  centre,   157 
Extirpation  of  the  liver,  336 

of  the  pancreas,  266 

of  the  thyroids,  268 
Extractives  of  the  blood,  50,  51 
Ext racts,  adrenal,  271 

ovai  ian,  '-'7  I 

testicular.  273 

thyroid,  269 
Exudations,  secretion  of,  215 

Fat,  affinity  of  cell  substance  for,  568 

nut  lit  l  vi-  history  of,  559 

origin  of,  from  carbohydrates,  352 
from  pi  oteid,  351,  560 
Pat-absorption,  influence  of  bile  on,  325 

mechanism  of,  318 
Pat-combustion,  equivalent  of,  365 
l'.ii  formation  in  the  body.351,560 
Fat-metabolism,  acetone  formation  in,  537 
Fats,  absorption  of,  in  the  stomach,  313 

action  of,  on  gastric  secretion,  241 

digest  ion  of,  305 


Fats,  dynamic  value  of,  475 

emulsification  of,  306 

gastric  digestion  of,  297 

nutritive  value  of,  277,  350 

of  feces,  319 

origin  of,   in  the  body,  351,  560 

relation  of,  to  glycogen  formation,  329 

synthesis  of,  from  fatty  acids,  558 
Fatty  acids,  monobasic,  532 

degeneration  in  phosphorus  poisoning,  514 
Feces,  composition  of,  319 
Fellic  acid,  543 
Fermentation,  alcoholic,  535 

lactic,  545 
Ferments,  unorganized,  279 
Ferratiu,  528,  529 
Ferric  phosphates,  528 
Ferrosulphide,  528 
Fever,  body-temperature  in,  472 

cause  of,  473 

effect  of,  on  blood  coagulation,  55 
on  the  respiratory  centre,  458 

heat  dissipation  in,  489 
Fibrillar  contraction  of  the  heart,  181,  183 
Fibrin  ferment,  56 

absence  of,  in  circulating  blood,  61 
nature  of,  57 
origin  of,  59 
preparation  of,  59 

mode  of  deposition  of,  54,  55 
Fibrin-globulin,  56 
Fibrinogen,  53,  54 
Fibrinoplastin,  56 

Fictitious  meal,  effect  of,  on  gastric  secretion,  239 
Filtration  processes  in  secretion,  213,  215 
Flavors,  nutritive  value  of,  359 
Fluorine,  occurrence  of,  510 
Food,  combustion  equivalent  of,  365 

definition  of,  275 

dynamic  value  of,  364 

effect  of,  on  respiratory  activity,  431 

energy  liberated  by,  474 

influence  of,  on  thermogeuesis,  484 

rate  of  movement  of,  in  the  intestines,  314 
Food -stuffs,  classification  of,  276 
composition  of,  278 
Liebig's  classification  of,  346 
Force    of    ventricular    systole    during     vagus 

stimulation,  163 
Formic  acid,  534 

aldehyde,  533 
Formose,  synthesis  of,  533 

Frequency  of  respiration,  conditions  affecting, 
425 
relation  of,  to  the  pulse-rate,  426 

Galactose,  562,  564 

Gall  bladder,  motor  nerves  of,  248 

Galvanic  current,  effect  of,  on  the  heart  apex, 

150 
Ganglion-cells  of  the  heart,  148 
Ganglion,  submaxillary,  219 
Gas  analysis,  421 
Gas-pump,  description  of,  420 
Gaseous  interchanges  in  the  lungs,  410,  417 

in  the   tissues,  419 
Gases,  absorption  of,  414 

in   tin-  large  intestine,  320 

in  the  blood,  respiratory  changes  in,  411 

of  the  saliva,  221 

law  of  partial  pressure  of,  413 

poisonous,  inhalation  of,  440 

solutions  of,  415 
Gastric  digestion  of  proteids,  292 
value  of,  299 

fistulas,  288 

glands,  histology  of,  237 


INDEX. 


589 


Gastric  glands,  secretory  changes  in,  242 

juice,  acidity  of,  289 

action  of,  on  carbohydrates,  296 

on  milk,  296 
antiseptic  property  of,  288 
artificial,  preparation  of,  291 
composition  of,  238,  288 
methods  of  obtaining,  287 
mineral  constituents  of,  530 

secretion,  inhibition  of,  241 
nervous  regulation  of,  239 
normal  mechanism  of,  240 
relation  of,  to  the  character  of  the  diet,  241 
stimulants  for,  241 
Gelatin,  digestion  of,  in  the  stomach,  297 

nutritive  value  of,  349 

proteid,  protecting  power  of,  567 
Gelatoses,  297 
Genio-hvoid  muscle,  function  of,  in  mastication, 

*372 
Gerhardt's  reaction,  537 
Gland,  adrenal,  271 

mammary,  262 

pancreatic,  231,  266 

parathyroid,  268 

parotid,  217 

sublingual,  217 

submaxillary,  217 

thyroid,  267 
Gland-cells,  selective  activity  of,  27 
Glands,  albuminous,  histology  of,  216 

Bru nner's,  243 

cutaneous,  257 

gastric,  237 

intestinal,  243 

Lieberkiihn's,  243 

mucous,  histology  of,  216 

salivary,  215 

sebaceous.  257 

serous,  definition  of,  216 

structure  of,  211 

sweat,  259 
Glauber's  salt,  522 
Globin,  37 

Globulicidal  action  of  serum,  36 
Globulins,  577 

Glomeruli,  renal,  secretory  function  of,  253 
Glossopharyngeal  nerves,  influence  of,  on  respi- 
ration, 462 
Glottis,  respiratory  movements  of,  408 
Glucosamin,  564 
Glucoses,  562 

synthesis  of,  563 
Glutamic  acid,  558 
Glutamin,  558 
Glutolin,  53 
I  Hutoses,  297 
Glycerin,  558 

aldehyde,  558 

phosphoric  acid,  559 
Glycerose,  558 
Glycocoll,  5:57,  543 

nutritive  history  of,  538 
Glycogen,  566 

amount  of,  in  the  liver,  327 

demonstration  <>f.  in  the  liver,  327 

distribution  of,  330 

effect  of  exercise  oil.  361 

of  starval  ion  on,  362 
of  sugars  on,  328 
function  of,  329 
in  the  muscles,  330 
origin  of,  326,  327 
properties  of,  327,  566 
Glycogen-elimination  of  the  liver,  265 
Glycogen-formation,  effect  of  proteid  diet  on,  328 
Glycogen-formers,  328 


Glycogenic  theory,  329 

Glycolysis,  354 

Glycolytic  enzyme,  280,  354 

origin  of,  267 
Glyco-proteids,  576,  578 
Glycosazones,  562 
Glyco-secretory  nerves,  248 
Glycoses,  562 

Glycosuria  after  pancreas  extirpation,  266,  563 
Glycu ionic  acid,  567 
Gmel in's  test  for  bile-pigments,  322,  574 
Goblet  cells,  216 
Goitre,  269 
Gout,  557 
Grammeter,  477 
Gram-molecular  solution,  67 
Guauin,  339,  554 
Guauidin,  550 
Giinzburg's  reagent,  508 

H^matin,  37,  44,  573 
Hsematogen,  356 

composition  of,  579 

nutritive  value  of,  528 
Hsematoidin,  44,  323,  574 
Hasniatopoiesis.  definition  of,  45 
Haematopoietic  tissues,  embryonic,  46 
Haeniatoporphyrin,  44,  574 
Htemerythrin,  578 
Haeinin,  44,  573 
Hsemochromogen,  37,  44,  573 
Haeruocyanin,  578 
Haemoglobin,  573 

absorption  spectra  of,  43 

action  of,  on  carbonates,  517 

affinity  of,  for  CO2,  417 

amount  of,  38 

compounds  of,  with  gases,  38 

condition  of,  in  the  corpuscles,  35 

crystals  of,  39 

decomposition  products  of,  37 

derivatives  of,  4 1 

distribution  of,  in  animals,  37 

elementary  composition  of,  37 

molecular  formula  of,  37,  38 

nature  of,  '■'<! 

oxygen  capacity  of,  416 
Hawking,  454 

Head,  vaso-motor  nerves  of,  204 
Heart,  anaemia  of,  183 

artificial  si  imulal  ion  of,  156 

augmentor  nerves  of,  167 

cause  of  rhythmic  beat  of,  148 

centripetal  nerves  of,  171 

changes  in  form  of,  1 13 
in  position  of,  1 14 
in  size  of,  1 12 

compensatory  pause  of,  156 

electrical  currents  of,  152 

erection  of,  1 14 

fibrillar  contraction  of,  181 

beat  produced  by,  108 
human,  oul  put  of  tbe.  106 

intrinsic  nerves  of,  148 
isolation  of,  1  18,  187 
lymphal  ics  of  t  be,  l  B6 

muscle,  atrophy  of,  after  section  of  the   vagi, 
L67 
conduction    of    the    contraction    wave    by, 

154 
rhythmicity  of,  151 
normal  stimulus  of,  151 

nutrition  of.  17!' 
Heart   beat,  abnormal  Sequence  of,  lr>2 

conduction   of,  from    auricles   to   ventricles, 

155 
effect  of  blood-supply  on,  186 


590 


INDEX. 


Beart  heat,  genesis  of,  149, 150 
heat  produced  by,  108 
rate  of,  121 
Heart-pause,  122 
position  of,  1 17 
pumping  action  of,  7^ 
refractory  period  of,  156 
Heart-sounds,  118 

suction-pump  action  of,  134 
tetanus  of,  L65 
vaso-motor  nerves  of,  206 
work  done  by  the,  1"7 
Heat-dissipation,  conditions  affecting,  485 

estimation  of,  l~(l 
Heal  dyspnoea,  441,  443 
expenditure  of,  476 
income  of,  475 
Heat-production,  amount  of,  364 
by  the  heart,  L08 
conditions  affecting,  482 
estimation  of,  481 

nlation  of,  to  respiratory  activity,  483 
Heat-regulation,  495 

source  of,  474 
Helico-proteid,  composition  of,  579 
Hemi-peptone,  decomposition  of,  by  trypsin,  303 

definition  of,  293 
Hemorrhage,  effect  of,  on  heniatopoiesis,  46 
fatal  limits  of,  63 
regeneration  of  the  blood  after,  63 
relation  of,   to  blood-pressure,  91 
saline  injections  after.  Hi 
Hemorrhagic  dyspnoea,  444 
Hepatin,  528 

Heredity,  physical  basis  of,  28 
Hezon-bases,  origin  of,  580 
Hexoses,  562 
Hibernation,     effect     of,     on     the     respiratory 

quotient,  438 
Hiccough,  455 

Higher  brain  centres  for  the  heart,  178 
Hippuric- acid,  nutritive  history  of,  339 
Histidin,  552 
II  istohsematin,  44,  578 
Hist  on,  580 

effect  of,  on  intravascular  clotting,  61 
Homogentisic  acid.  570 
Homothermous  animals,  467 
Hiifner's  method  of  urea  determination,  549 
Hydra-mia  from  saline  injections,  69 
Hydramic  plethora,  effect  of,  on  lymph  secre- 
tion, 74 
Hydration,  nature  of  the  process  of,  503 
Hydriodic  acid,  509 
Hydrobilirubin,  320 
Hydrobromic  a<  id,  509 
Hydrocarbons,  saturated,  531 
Hydrochloric  acid,  occurrence  of,  507 
of  the  gastric  juice,  238 
preparation  of,  507 
properties  of.  50S 
secretion  of,  289 
testa  for,  508 
Hydrocumaric  acid.  570 
Hydrocyanic-  acid,  542 
Hydrofluoric  acid,  circulation  of,  in  tho  body, 

510 
Hydrogen,  inhalation  of,  440 
occurrence  of,  499 
peroxide,  505 
preparation  of,  500 
properties  of,  500 
Hydrolysis  by  enzyme  action,  282 
definition  of,  504 
of  fats,  305 
of  proteids.  292 
1 1;  il  i oquinone,  569 


Hypertonic  solutions,    physiological    definition 

of,  69 
Hypertonicity,  definition  of,  37 
Hyperpnoea,  1 10 

from  muscular  activity.  442 
Hypophysis  cerebri,  function  of,  273 
Hypotonicity,  definition  of,  37 
II  \  poxanthin,  553 

relation  of,  to  uric  acid  formation,  338 

Ice  calorimeter,  principle  of,  504 
Icterus.  249,  544 
Idio-ventricular  rhythm,  152 
Imbibition  of  water,  504 
Indol,571 

elimination  of,  340 
occurrence  of,  in  feces,  320 
Inferior  laryngeal  nerve,  respiratory  function 
of,  iii4 
mesenteric  ganglion,  reflex  activity  of,  392 
Inflammation,  emigration  of  leucocytes  in,  83 
Iufra-hyoidei  muscles,  405 
Infundibular  body,  function  of,  272 
Inhibition  of  the  heart,  reflex,  172 
Inhibitory  centre,  cardiac,  localization  of,  176 
tonus  of,  176 
centres,  respiratory.   1~>7 
nerves  of  the  heart,  161 
of  the  intestines,  385 
of  the  pancreas,  233 
of  the  spleen,  333 
of  the  stomach,  382 
Innervation  of  the  blood-vessels,  192 

of  the  heart,  148 
Inorganic  salts  of  the  blood,  50 
of  urine,  341 

relation  of,  to  blood  coagulation,  56,  57 
to  the  heart  beat,  151,  189 
Inosit,  573 
Inspiration,  enlargement  of  the  thorax  in,  398 

muscles  of,  398,  404 
Inspiratory  centre,  457 
Intercostaies  muscles,  respiratory  action  of,  402, 

407 
Intermittent  pulse,  141 
Internal  secretion,  definition  of,  265 
of  the  adrenal  bodies,  272 
of  the  kidneys,  274 
of  the  liver,  265 
of  the  ovaries,  274 
of  the  pancreas,  266 
of  the  pituitary  body,  273 
of  the  testis.  273 
of  the  thyroids,  270 
Intestinal  contents,  reaction  of,  310 
digestion,  299 
juice,  243 

movements,  382  385 
Intestines,  innervation  of,  384 
intrinsic  nervous  mechanism  of,  384 
large,  absorption  in  the,  314 
peudular  movements  of,  384 
peristalsis  of,  382 
putrefactive  changes  in  the,  310 
small,  absorption  in  the,  313 
vaso-motor  nerves  of,  206 
Intracardiac  pressure,  H>7,  125,  126 
methods  of  measuring,  129,  130 
Intrapulmonary  pressure,  408 
Intrathoracic  pressure,  397,  409 
Intravascular  clotl  Ing,  60,  61 
Intrinsic  nerves  of  the  heart,  148 
Invertase,  occurrence  of,  308 
Invertinc,  definition  of,  280 
Iodine,  509 

todothyrin,  properties  of,  270 
Ionic  theory  of  solutions,  67 


INDEX. 


591 


Iron,  amount  of,  in  haemoglobin,  39 

excretion  of,  530 

inorganic,   absorption  of,  529 

nutritive  history  of,  528 

occurrence  of,  528 

synthesis  of,  into  haemoglobin,  529 

salts,  excretion  of,  356 
nutritive  value  of,  356 
Irradiation  of  medullary  centres,  201 
Irrigating  fluids  for  the  isolated  heart,  189,  191 
Irritability  of  living  matter,  18 
Ischaeniia  of  heart  muscle,  181 
Iso-butyl  alcohol,  539 
Iso-butyric  acid,  539 
Iso-dynamic  equivalence  of  foods,  365 
Isolated  apex  of  frog's  heart,  188 
Isolation  of  the  heart,  148,  191 
I.somaltose,  565 
Iso-pentyl  alcohol,  539 
Isotonic  solutions,  36,  69 
Isotonicity,  36,  68 
Iso-valerianic  acid,  539 

Jaundice,  249,  544 
Jecorin.  564 

Karyokinesis,  20 
Katabolism,  definition  of,  19 
Keratin,  580 

Ketoses,  definition  of,  561 

Kidneys,  blood-flow  through  the,  255 

histology  of,  249 

internal  secretion  of,  274 

nerve-endings  in,  251 

vaso-motor  nerves  of,  207,  256 
"  Klopf-versuch  "  of  Goltz,  175 
Kymograph.  89 

Lactalbumin,  261 

Lacteal  vessels,  318 

Lacteals,  absorption  through  the,  311 

Lactic  acid,  545 

fermentation,  545 
occurrence  of,  in  the  stomach,  289 
Lacto-globulin,  261 
Lactose,  262,  565 
Laky  blood,  35 
Laugerhans,  bodies  of,  232 
Lanolin,  257,  575 

Large  intestine,  digestion  in  the,  309 
Latent  heat,  definition  of,  504 

period  of  cardiac  accelerator  nerves,  170 
of  heart  muscle,  153 
of  vagus-stimulation,  162 
Latham's  hypothesis  of  the  structure  of  pro- 
toplasm, 24 
Laughing,  454 
Lecithin.  559 

amount  of,  in  the  blood,  51 

occurrence  of,  325 

of  bile,  245 

of  milk.  261 
Leech  extract,  effect  of,  on  blood  coagulation,  62 

lymphagogic  action  of,  73 
Leucin,  chemical  properties,  540 

formation  of.   in  fcryptic  digestion,  303 

nutritive  history  of,  540 

occurrence  of,  540 
Leucocytes,  behavior  of.  in  blood  capillaries,  82 

classification  of,   17.  48 

emigration  of,  83 

from  the  thymus  <,dand,  composition  of.  51 

functions  of.    18 

influence  of.  on  blood-plasma,  49 
origin  of,  49 
Leucocythaemia,  fatty  acids  in,  530 
nnrin  bases  excreted  in,  557 


Leucouuclein,  effect  of,  on   intravascular  clot- 
ting, 61 
Levatores  ani  muscles,  expiratory  action  of,  407 

costarum  breves,  inspiratory  action  of,  402 
Levulic  acid,  538 
Levulose,  oil.' 

fate  of,  in  pancreatic  diabetes,  267 

occurrence  of,  564 

oxidation  of,  in  diabetes,  564 
Lieberkuhn's  crypts,  histology  of,  243 
Liebitr's  method  of  urea  determination,  549 
Life,  general  hypothesis  of,  25 
Ligatures  of  Staunius,  178 
Limbs,  vaso-motor  nerves  of,  209 
Lipase,  305 
Lipochromes,  574 
Liqueurs,  535 

Living    matter,    elementary    constituents     of, 
499 

general  properties  of.  18  m 

molecular  structure  of,  23 
Liver,  defensive  action  of,  against  intravascular 
clotting,  61 

extirpation  of  the,  336 

functions  of,  320 

histology  of,  244,  321 

internal  secretion  of,  265 

lymph  formation  in,  73 

nerve-endings  in,  245 

secretory  function  of,  244 
nerves  of,  247 

urea  formation  in,  331 

vaso-motor  nerves  of,  206 
Loew's    hypothesis  of    the    structure   of   pro- 
toplasm, 23 
Loop  of  Heule,  250 
Lungs,  capacity  of,  427 

nerve-supply  of,  465 

structure  of,  396 

vaso-motor  nerves  of.  205 
Lunulas  of  the  semilunar  valves,  111 
Lutein,  574 

Luxus  consumption,  348 
Lymph,  33 

amount  of,  146 

definition  of.  70 

formation  of,  71 

gases  of,  419 

mechanical  theory  of  the  origin  of  the,  75 

movement  of,  71,  146 

pressure  of.  1  hi 

secretion  of,  214 
Lymphagogues,  action  of,  73,  74 
Lymphatics  of  the  heart.  186 
Lymphatic  system,  nature  of,  145 
Lymph  glands.  1  16 
Lymphocytes,  18 
Lysatin.  551 
Lysatinin,  relation  of,    to  urea  formation,  337, 

551 
Lysin,  552 

Magnesium  carbonate,  527 

nutritive   history  of,  527 
occurrence  of.  527 
phosphates,  527 

Malic  acid.  558 

Malpighian  corpuscle  of  fche  kidnev,  structure 

of.  249 
Maltase,  280,  565 

in  starch  digestion,  285 

occurrence  of.  308 
Mammary  glands,  histological  changes  in.  262 

normal  secret  ion  of,  264 

secretory  nerves  of,  263 

structure  of.  '-'61 
Manuose.  562 


592 


INDEX. 


Manometer,  differential,  131 

elastic,  127 

maximum,  107 

mercurial,  87 
Marsh  gas,  532 
Masseter  muscle,  372 
Mastication,  372 
"  Mastzellen,"  relation  of,  to  colostrum  corpus- 

cies,  -'<;:; 

Meal  extracts,  physiological  action  of,  359 

Meals,  composition  of,  278 

Meconium,  biliary  salts  in,  544 

Melanins,  574 

M<  licyl  alcohol,  540 

Mercapturic  acids,  547 

Mercury  manometer,  description  of,  87 

Metabolism,  conditions  influencing,  359 

definition  of,  20 

during  sleep,  361 

during  starvation,  362 

effect  of  temperature  on,  362 

influence  of  the  cell-nucleus  on,  22 

methods  of  estimating,  343 
Metaphosphoric  acid,  514 
Methane,  origin  of,  532 
Met  haemoglobin,  44,  57.'! 
Methods,  physiological.   .'!1 
Methyl  amido-acetic  acid,  538 
Methylamine,  541 
Methyl  mercaptan,  534 

selenide,  534 

telluride,  534 

violet,  in  testing  for  mineral  acids,  289 
Micellae,  definition  of,  25 
Micturition,  389 

centre  for,  391.  393 

nervous  mechanism  of,  392 
Milk,  composition  of,  261 

mineral  constituents  of,  530 

normal  secretion  of,  264 
Milk-sugar,  565 

Millon's  reaction  for  proteids,  576 
nature  of,  569 
with  phenol,  569 
Mineral  acids,  tests  for,  289 

constituents,  amount  of,  in  the  tissues,  530 
Mitosis,  •-'ii 

Molecules,  physical  and  physiological,  25 
Mononuclear  leucocyte-.    I- 
Morphin,  effeel  of,  on  body-temperature,  472 
Mouth,  temperature  in  the,  469 
Mucin  of  bile,  325 

of  gastric  .juice.  288 

of  saliva,  2H.'{ 

physiological  value  of,  221 

properties  of.  578 

secretion  of.  217 
Mucous  glands,  histology  of,  216 
Mailer's  experiment,  152 
Mu n\ icl.  555 
Muscarin,  543 

act  ion  of.  on  the  heart,   150 
Muscle,  digastric.  372 
genio-hyoid,  372 
glycogenic  function  of,  330 
involuntary,  properties  of,  370 
masseter,  372 

mineral  constituents  of,  530 
mylo-hyoid.  372 
obliquus  externus,  407 

interniis,   11)7 
pterygoid,  external,  372 

internal,  372 
pyramidalis,  407 
temporalis,  :'>72 
transversalis  abdominis,  407 
trapezius,    105 


Muscles,   abdomiuales,  action   of,  in  vomiting, 
387 
respiratory  function  of,  407 
erectores  spina1,  405 
expiratory,  407 
glycogen  of  the,  330 
infrahyoidei,  405 
inspiratory,  399,  405 
intercostal.  402,  407 
levatores  ani,  407 

costarum,  402 
of  mastication,  372 
pectorales,  405 
quadrati  lumhorum,  399 
rhomboidei,  405 
scalei,  401 

serrati  postici,  399,  402 
st e in o-cle id 0- mastoid,  404 
thermogenic  function  of,  490 
triangulares  stern i,  407 
vaso-motor  nerves  of,  210 
Muscular  exercise,  effect  of,  on  metabolism,  359 
on  the  pulse  rate,  121 
on  the  rate  of  respiration,  426 
on  the  respiratory  exchanges,  433 
on  the  respiratory  quotient.  438 
on  the  sweat  glands,  260 
on  the  venous  circulation,  95 
Mycoderma  aceti.  537 
Mylo-hyoid  muscle,  372 

Myogonic  theory  of  the  causation  of  the  heart- 
beat, 150 
Myohsematin,  578 
Myosin,  absorption  of,  315 
Myxcedema,  269 

Native  albumins.  577 

Negative  pressure  in  the  auricles,  137 

in  the  heart,  98 

in  the  thorax,  95 

in  the  veins,  94 
variation  of  the  beating  heart,  153 
Nerve,  auriculotemporal,  218 
chorda  tympani,  194,  219 
coronary,  of  the  tortoise,  164 
depressor,  172,  203 
facial,  secretory  fibres  of,  219 
glossopharyngeal,  secretory  fibres  of.  218 
Jacobson's,  218 

lingual,  secretory  fibres  of,  219 
small  superficial  petrosal.  218 
vagus,  cardiac  branches  of,  159 

gastric  branches  of,  381 

intestinal  branches  of,  385 

pulmonary  branches  of,  465 

respiratory  functions  of.  459 

secretory  fibres  of,  232,  239 

trophic  influence  of,  on  the  heart,  166 
Nerve-endings  in  the  liver,  245 

in  the  salivary  glands.  220 
Nerves,  augmentor,  of  the  heart,  167 
cardiac,  1  Is 

cervical  sympathetic.  193 
depressor,  of  the  heart.  172 
of  the  bile  vessels,  248 

phrenic,  163 

septal,  of  the  frog's  heart,  166 

splanchnic,  17.'! 

trigeminal,  463 
N'ervi  erigentes,  intestinal  branches  of,  385 
Neukomiu's  test  for  bile  acids,  545 
Neuridin,  543 
Neu rin,  543 

Neurogenic  theory  of  the  causation  of  the  heart- 
beat. 149 
Neuro-keratin,  580 
Neutral  salt-,  effect  of,  on  blood  coagulation,  62 


INDEX. 


593 


Neutrophils,  47 

Nicotin.  action  of,  on  intestinal  movements,  384 

on  secretory  nerves,  229 
Nitric  oxide,  512 

haemoglobin,  39,  512 
Nitrogen  equilibrium,  definition  of,  344,  512 
history  of,  in  the  body,  512 
inhalation,  440 
occurrence  of,  510 
of  the  feces,  320 
preparation  of,  510 
tension  of  the  blood,  417 
Nitrogenous  equilibrium,  definition  of,  344,  512 
excreta  of  milk,  262 

of  sweat,  259 
extractives  of  the  spleen,  333 
metabolism,  estimation  of,  343 
Nitrous  oxide,  inhalation  of,  440 

properties  of,  512 
Nceud  vital,  456 
Nucleic  acid,  579 
Nuclein  bases,  552 

composition,  556,  579 
Nucleo-histon  of  the  blood-plates,  49 

relation  of,  to  intravascular  clotting,  61 
Nucleo-proteids,  classification  of,  577 

properties  of,  579 
Nucleus,  functions  of,  22 

relation  of,  to  oxidation,  503 
Nutrition  of  living  matter,  18 
Nutritive  value  of  albuminoids,  349 
of  carbohydrates,  353 
of  fats,  350 
of  proteids,  276,  345 
of  salts,  354 
of  water,  354 

Obliquus  extern  us,  respiratory  action  of,  407 
internus,  respiratory  action  of,  407 

Occlusion  of  the  bile-duct,  effect  of,  249 

(Edema,  148 

(Esophagus,  deglutition  in  the,  374 

Oils,  effect  of,  on  gastric  secretion,  241 
on  pancreatic  secretion,  236 

Olefines,  542 

Oleic  acid,  541-560 

Oncometer,  255 

Oophorin  tablets,  action  of,  274 

Opening  of  the  chest,  effect  of,  on  heart,  115 

Opium,  effect  of,  on  respiratory  rhythm,  425 

"  Organeiweiss,"  346 

Ornithiu,  552 

Orthophosphoric  acid,  514 

Osazones  of  glycoses,  562 

Osmosis,  definition  of,  65 
relation  of,  to  secretion,  213 

Osmotic  pressure,  definition  of,  65 
method  of  determining,  67,  68 
relation  of,  to  concentration,  66 

Osones.  preparation  of,  562 

Osteomalacia,  524,  ■".•.'.". 
ovariotomy  in,  271 

( Osteoporosis,  525 

Ovariotomy,  effects  of,  274 

Ovaries,  internal  secretion  of,  274 

Oxalate  solutions,  effect  of,  on  blood   coagula 
tion,  63 

<  Oxalic  acid,  557 

<  Oxaluric  acid,  555 
Oxidases,  281 
Oxidation,  501 

physiological,  Hoppe-Seyler'a  theory  of.  505 
Traube's  theory  of,  502 
Oxidizing  enzymes,  2S0 
< )xybutyric  acid.  5 Id 
Oxycholin,  543 
Oxygen,  alveolar  tension  of,  413 

38 


Oxygen,  occurrence  of,  500 
preparat  ion  of,  501 
proper)  ies  of,  501 
tension  in  the  blood,  415 

respiratory  effects  of,  varying,  440 
Oxygen-absorption,  coefficient  of,  415 
conditions  affecting,  429 
cutaneous,  122 
estimation  of,  428 
( Oxygen-dyspnoea,  444 
Oxyhemoglobin,  composition  of,  38 

dissociation  of,  415,  501 
Oxyntic  cells  of  gastric  glands,  237 
Oxyphenyl-acetic  acid,  570 
Oxyphenyl-amido-propionic  acid,  570 
Oxyphiles,  47 
Ozone  inhalation,  440 
preparation  of,  502 
properties  of,  502 

Palmitic  acid,  541 
Pancreas,  anatomy  of,  231 
extirpation  of,  266 
grafting  of,  267 
histology  of,  231 
innervation  of,  232 
internal  secretion  of,  266 
mineral  constituents  of,  530 
secretory  changes  in,  233 
vaso-motor  nerves  of,  207 
Pancreatic  diabetes,  267,  353,  563 
fistulas,  preparation  of,  300 
juice,  amylolytic  action  of,  305 
artificial,  301 
collection  of,  300 
composition  of,  232,  299 
fat-splitting  power  of,  305 
secretion,  composition  of,  232,  299 
histological  changes  during,  233 
nervous  mechanism  of,  232 
normal  mechanism  of,  235 
reflex  character  of,  236 
relation  of,  to  the  character  of  the  food,  237 
Papain,  280 
Papillary  muscles,  110 
Parabamic  acid,  555 
Paracasein,  296 
Paraffins,  531 
Paraformic  aldehyde,  533 
Paraglobulin,  amount  of,  in  the  blood,  53 
composition  of,  53 
functions  of,  53 
origin  of,  53 
properties  of,  53 
Paralytic  secretion,  229 
Parapeptone,  definition  of,  292 
Paranuclein,  579 
Parathyroids,  anatomy  of,  268 

function  of,  269 
Parotid  gland,  anatomy  of,  217 

innervat  ion  of,  218 
I'ate  de  I'oie  gras,  560 

Pause,  compensatory,  of  the  heart,  156 
Pauses,  respiratory,  124 
Pectoral  muscles,  respiratory  action  of,  105 
Pendular  movements  of  the  intestines,  38  1 
Pcntamel  hylene-diamin,  543 

Pentoses.  562 
Pepsin,  237,  238 

effect  of,  oil  blood  coagulation,  63 

preparation  of,  291 

proper!  Les  of,  290 
Pepsin-hydrochloric  acid,  action  of,  292 
Pepsinogen  granules,  2 12 
Peptic  digestion,  292,  294 

Pepton-injection,  effect  of,  on  lvmph  formation, 
73 


594 


IXDEX. 


Pepton-injection,  toxicity  of,  316 
Peptones,  absorption  of,  in  the  stomach,  313 

,1. ■Unit ion  of,  292,  295 

effecl   of,  on  blood  coagulation,  62 

proper!  ies  of,  294,  577 
Perfusion  cannula.  187 
Peripheral  reflex  centres,  178 
Peristalsis,  definition  of,  372 

intestinal,  382 

of  the  stomach,  :;7!> 

of  the  ureters.  389 
Permeability  of  the  capillary  walls,  70 
Peroxide  of  hydrogen,  505 
Pettenkot'er's  reaction  for  hile  acids,  324,  544 
Pexinogen  granules,  242 
Ptlimer's  hypothesis  of  the  structure  of  proto- 

plasm,  '.'•'> 
Phagocytosis,  48 

Pharynx,  deglutition  in  the,  373 
Phenaceturic  acid,  569 
Phenol,  569 

elimination  of,  340 
Phenyl-acetic  acid.  569 
Phloridzin  diabetes,  563 
Phosphates,  51  1 
Phosphoric  acid,  salts  of,  514 
Phosphorus,  nutritive  history  of,  515 

occurrence  of,  513 

peroxide,  514 

poisoning,  513 

preparation  of,  513 

properties  of,  513 
Phrenic  nerves,  463 
Physical  molecules,  definition  of,  25 
Physiological  division  of  labor,  22 

molecules,  25 

salt  solution  in  transfusions,  64 
Physiology,  definition  of,  17 

human,  definition  of,  30 

methods  employed  in,  30 

subdivisions  of,  17,  29 
Pigments,  biliary,  45,  245.  322,  530,  574 

blood-,  37,  44,  573 
Pilocarpin,  action  of,  on  salivary  glands,  229 

on  sweat-glands,  260 
Pilomotor   mechanism,   relation  of,  to  thermo- 
lysis, 494 
Pituitary  body,  anatomy  of,  272 
functions  of,  273 
internal  secretion  of,  273 

extracts,  action  of,  272 
Plain  muscle,  histology  of,  369 
physiology  of,  370 
tune  of,  371 
Plant-cells,  assimilation  in,  18 
1'lasnia  of  blood.  :;:;,  .">() 

oxygen  absorption-coefficient  of,  416 
Plastic  food-stuffs,  definition  of,  346 
Plethysmograph,  196 
Pneumatic  cabinet,  453 
Pneumogastric  nerve  (see  Vagus). 
pulmonary  branches  of,  465 
respiratory  function  of,  459,  460 
Pneumograph,  123 
Poikilothermous  animals,  467 
I'olynueleatcd  leucocytes.    IS 

Polypncea,  441 

Portal  vein,  vaso-motor  nerves  of,  209 

Positive    variation    of   the   heart  during  vagus 

stimulation,  164 
Post-mortem  rise  of  temperature,  497 
Potassium  carbonates,  nutritive  history  of,  520 
chlorides,  nutritive  history  of,  519 

cyanide,  5 12 
occurrence  of,  519 

phosphates,  nutritive  history  of,  520 
illation  of.  to  heart  muscle,  151 


Potassium  salts,  toxicity  of,  520 
sulphocyanide,  detection  of,  284 
occurrence  of,  283,  542 
of  the  urine,  507 

thiocyanide,  512 

Potential  energy  of  food,  364 
Pressor  nerves,  202 
Pressure,  intracardiac,  107 

intrathoracic,  396,  409 

intraventricular,  125 

of  the  lymph,  146 
Propeptones,  definition  of,  292 
Propionic  acid,  538 
Propyl  alcohol,  536,  538 
Protagon,  559 

Protamine,  nature  and  origin  of,  24 
Protamins,  properties  of,  580 
Proteid,  affinity  of  cell  substance  for,  568 

circulating,  definition  of,  346 

metabolism  during  starvation,  363 
effect  of  muscular  work  on,  360 
end-products  of,  337 
Proteid-absorption,  mechanism  of,  316 
Proteids,  absorption  of,  315 

classification  of,  576 

color  reactions  of,  576 

combined,  classification  of,  579 

combustion  equivalent  of,  365 

diffusion  of,  70 

dynamic  value  of,  475 

effect  of,  on  glycogen  formation,  328 

gastric  digestion  of,  292 

general  reactions  of,  575 

general  significance  of,  24 

living,  theoretical  structure  of,  23,  24 

molecular  structure  of,  581 

nutritive  value  of,  276,  345 

of  milk,  261 

of  the  blood,  49,  50 

origin  of  fat  from,  351 

osmotic  pressure  of,  69 

putrefaction  of,  in  the  intestines,  310 

rapidity  of  oxidation  of,  347 

simple,  classification  of,  576 

substitutes  for,  in  the  diet,  348 

synthesis  of,  518,  582 

tryptic  digestion  of,  303 

vegetable,  577 
Proteose  injection,  effects  of,  316 
Proteoses,  definition  of,  292 

properties  of,  577 
Proteolysis,  293 

tryptic,  303 

value  of,  315 
Proteolytic  enzymes,  definition  of,  280 
Protoplasm,  17,  499 
Prothrombin,  58 
Pseudo-mucoid,  578 
Pterygoid  muscles,  372 
Ptomaines,  chemical  structure  of,  542 
Ptyalin,  221,  280 

action  of.  284,  2-6,  566 

occurrence  of.  28  1 
Pulmonary  circulation,  78,  103 
innervation  of,  205 

ventilation,  forces  concerned  in,  413 
Pulse,  arterial,  cause  of,  93 
celerity  of,  142 
definition  of,  139 
dicrotic  wave  of,  143 
extinction  of,  94 
frequency  of,  121,  141 
regularity  of,  111 

respiratory  variations  in  the  rate  of,  451 
size  of,  111 
tension  of,  141 
transmission  of,  140 


INDEX. 


595 


Pulse,  relation  of,  to  body-temperature,  171 

respiratory,  96 
Pulse-curve,  142 

Pulse-rate,  diurnal  variations  of,  121 
Pulse-volume  of  the  heart,  definition  of,  105 
Purin.  553 

bases,  552 

in  leucocythtemia,  557 
Putrefaction,  intestinal,  products  of,  310 
Putrescin,  543 
1'yin,  579 

Pyramidalis  muscle,  expiratory  action  of,  407 
Pyridin,  571 
Pyrocatechin,  569 

QUADRATI  lumborum,  respiratory  action  of,  399 
Quinine   hydrochlorate,   action   of,  on  salivary 
glands,  222 

Rarefied  air,  respiration  of,  452 
Eate  of  conduction  in  heart  muscle,  154 
of  heart-beat,  variations  of,  121 
of  progress  of  the  food  in  the  intestines,  314 
of  respiratory  movements,  425 
of  transmission  of  the  pulse,  140 
Reaction,  influence  of,  on  action  of  ptyalin,  286 
of  bile,  322 
of  blood,  34 
of  gastric  juice,  288 
of  intestinal  contents,  310 
of  pancreatic  juice,  232,  300 
of  succus  entericus,  308 
of  sweat,  342 
of  urine,  250,  334 
Rectus  abdominis,  expiratory  action  of,  407 
Red  corpuscles,  behavior  of,  in  the  capillaries,  81 
color  of,  35 
composition  of,  51 
disintegration  of,  45 
form  of,  35 
function  of,  35 
number  of,  35 
origin  of,  45,  46,  333 
size  of,  35 
structure  of,  35 

variations  in  the  number  of,  46 
Reduction,  502 

processes  in  the  animal  body,  536 
Reflex  acceleration  of  the  heart,  177 
coughs,  455 
discharge  of  bile,  248 
inhibition  of  the  heart,  172 
secretion  of  gastric  juice,  239 
of  pancreatic  juice,  236 
of  saliva,  230 
viiso-motor  changes,  202 
Reflexes   through    sympathetic  ganglia,   vaso- 
motor, 200 
Refractory  period  of  the  heart,  156,  158 
Regeneration  of  blood  after  hemorrhage,  63 
Rennin,  238 
action  of,  on  milk,  296 
occurrence  of,  in  gastric  juice,  295 
of  the  kidneys,  274 
preparation  of,  295 
Reproduction  of  living  matter,  18,  20 
Reproductive  organs,  vaso-motor  nerves  of,  208 
Residual  air,  definition  of,  427 
Respiration,  artificial,  446 
associated  movements  of,  408 
cutaneous,   122 
definition  of,  395 
heat  dissipated  in,  488 
intensity  of,  129 
internal,  422 

nervous  mechanism  of,  455 
rhythm  of,  423 


Respiratory  activity,  conditions  affecting,  429 
centres,  455 

afferent  nerves  to,  459 
conditions  influencing  the,  458 
foetal,   Ml 

rhythinicity  of,  458 
food-stuffs,  definition  of,  346 
movements,  circulatory  effects  of,  447 
duration  of,  424 
effect  of,  on  blood-pressure,  448 
on  venous  circulation,  95,  96 
frequency  of,  425 
special,  453 
nerves,  afferent,  460 

efferent.  463 
pauses,  424 
pressure,  408 
quotient,  410 

during  hibernation,  434 
relation  of,  to  the  diet,  353 
variations  of,  437 
sounds,  409 
Resuscitation  from  drowning,  445 
Rete  mirabile  of  the  Malpighian  corpuscles,  249 
Rh  am  nose,  562 
Rheometer,  99 

Rhomboideus  muscles,  respiratory  action  of,  405 
Rhythm  of  the  respiratory  movements,  423 
Rhythmic  activity  of  the  vaso-coustrictor  cen- 
tre, 201 
Rhythinicity  of  the  heart,  abnormal,  152 

cause  of,  148 
Ribs,  respiratory  movements  of,  400 
Rickets.  351!,  525 
Right  lymphatic  duct,  145 
Ringer's  solution  for  the  heart,  190 
Riviuus,  ducts  of,  217 
Roy's  tonometer,  188 

Saccharose,  564 
Saliva,  composition  of,  220,  283 
mineral  constituents  of,  530 
properties  of,  220,  283 
uses  of,  286 
Salivary  corpuscles,  283 
glands,  215 
anatomy  of,  217 
histology  of,  219 
histological  changes  in,  226 
nerves  of,  218,  221 
vaso-motor  nerves  of,  222 
secretion,  action  of  drugs  on,  229 
normal  mechanism  of,  230 
Salkowski's  reaction  for  cholesterin,  575 
Sahnin,  580 
Salt-licks,  355 

Salt  solution,  physiological,  injection  of,  64 
Salts,  absorption  of.  318 
lympbagogic  act  ion  of,  73 

nutritive  value  of,  27l>.  354 
Saponification  of  fats,  306,  558 
Saprin,  543 
Sarcin,  553 
Sarco-lactic  acid,  546 
Sarcosin,  538 

Scaleni  muscles,  inspiratory  action  of.  401 
Scombrin,  ">^'> 

Sebaceous  glands,  structure  <<(,  257 

secretion,  composition  of,  342 

function  of,  258 
physiological  value  of,  312 

Sebum,  composil  ion  of,  257 

Secreting  glands,  electrical  changes  in,  231 
histological  changes  in,  226 

Secret  ion,  anl  ilytic,  230 
biliary,  248 
capillaries  of  the  gastric  glands,  238 


596 


INDEX. 


Secretion,  definition  of.  211 
gastric,  240 

histological  changes  during,  226 
internal,  definition  of,  211 
intestinal,  243 
mammary,  264 
mechanism  of,  213 
panel eal ic,  235 
paralytic,  229 

psychical,  of  gastric  juice,  239 
relation  of,  to  intensity  of  stimulus,  223 
salivary.  230 
sebaceous,  257,  342 
sweat,  259 
urinary,  251 
Secretions,  general  characteristics  of,  213 
Secretogogues  for  the  gastric  glands,  359 
Secretory  centre,  salivary,  230 
fibres  proper,  definition  of,  224 
nerves,  evidence  for,  222 
mode  of  action  of,  225 
of  the  adrenal  bodies,  272 
of  the  kidneys.  251 
of  the  liver,  247 
of  the  mammary  glands,  263 
of  the  pancreas,  232 
of  the  stomach,  239 
of  tli<'  swear  glands,  259 
salivary,  endings  of,  220 
significance  of,  214 
stimulation  of,  222 
Semilunar  valves.  110 

Sensory  nerves,  influence  of,  on  respiration.  463 
of  the  heart,  172 

relation  of,  to  the  respiratory  centre,  459 
reflex  influence  of,  on  the  pulse-rate,  175 
Septal  nerves  of  the  frog's  heart,  166 
Serous  cavities,  146 

Serrati  postici   inferiores,   respiratory  function 
of,  :>w 
superiores,  inspiratory  action  of,  402 
Serum,  bactericidal  action  of,  36 
glohulicidal  action  of,  36 
osmotic  pressure  of.  68 
toxicity  of,  36 
Serum-albumin,  action  of,  on  carbonates,  517 
amount  of,  in  the  hlood,  52 
composition  of,  52 
functions  of.  52 
properties  of,  52 
Sex,  influence  of,  on  heat  production,  482 
on  pulse-rate,  121 
on  respiration,  430 
relation  of  body-temperature  to,  470 
Shivering.  362,   KM 
Silicic  acid,  properties  of,  r>l!) 
Silicon,  519 
Simple  proteids,  576 
Sinuses  of  Valsalva,  1 1 1 
Size,  influence  of,  mi  pulse-rate,  121 
Skatol,  572 
elimination  of.  340 
occurrence  of,  in  feces,  320 
Skin,  functions  of.  341 
glands  of,  '.'57 

Sleep,  etlect  of.  on  metabolism,  361 
on  the  respiratory  quotient,  438 
on  respiration,  124 
Smegma  prseputii,  257 
Sneezing,   154 
Snoring,  455 
Sobbing,  454 
Sodium  ammonium  phosphate,  523 

carbonates,  522,  523 

chloride,  nutritive  history  of,  521 

phosphates,  522 

sulphate,  522 


Special  respiratory  movements,  453 
Specialization  of  function,  21 
Specific  gravity  of  blood,  34 
of  blood-corpuscles,  34,  35 
of  urine,  251 
heat,  definition  of,  477 
of  the  human  body,  504 
Spectroscope,  40 
Spectrum,  definition  of,  40 
of  CO-hsemoglobin,  44 
of  haemoglobin,  42 
of  oxyhemoglobin,  41 
solar,  41 
Spermaceti,  540 

Spermin,  physiological  action  of,  273 
Sphincter  antri  pylorici,  377 
pylori,  377,  381 ' 
urethrse,  390 
vesicae  internus,  390 
Sphincters  ani,  386 
Sphygmograur,  143 
Sphygmograph,  142 
Sphygmomanometer,  141 
Sphygmometer,  141 

Spinal  centres  for  vaso-motor  nerves,  199 
Spirometer,  427 

Splanchnic  nerves,  gastric  fibres  of,  382 
influence  of,  on  blood-pressure,  173 

on  respiration,  403 
intestinal  fibres  of,  385 
stimulation  of,  173 
Spleen,  composition  of,  333 
function  of,  322 
innervation  of,  333 
movements  of,  322 
vasomotor  nerves  of,  207 
Stannius's  ligatures,  178 
Starch,  566 

digestion  of,  2^4,  305 
hydrolysis  of,  by  acids,  286 
by  amylolytic  ferments,  285 
Starvation,  etlect  of.  on  metabolism,  362 
glycogen  disappearance  during,  331 
nutrition  during,  350 
phosphorus  excretion  in,  516 
potassium  excretion  in,  520 
Steapsin,  232,  280 

den stration  of,  306 

occurrence  of,  305 
Stearic  acid,  541 
Stenson's  duct,  217 
Stereo rin,  575 

Sterno-cleido-mastoid    muscles,  respiratory    ac- 
tion of,  404 
Sternum,  respiratory  movements  of,  401 
Stethograph,  423 
Stimulants  of  the  sweat  glands,  260 

physiological  action  of,  357 
Stimuli,  artificial,  effect  of,  on  I  lie  heart,  156 
Stokes's  reagent,  composition  of,  43 
Stomach,  absorption  in,  312 
extirpation  of,  299 
glands  of,  237 

immunity  of,  to  its  own  secretion,  2i)7 
innervation  of,  381 
movements  of.  377.  378 
musculature  of,  377 
Strom uhr  of  Ludwig,  99 
St  rontium,  526 

Strychnine,  etlect  of,  on  body-temperature,  472 
Sturin,  580 

Sublingual  gland,  anatomy  of,  217 
Submaxillary  gland,  anatomy  of,  217 
Succinic  acid,  557 
SUCCUS  entencus,  243 

:n  lion  of,  on  carbohydrates.  309 
collection  of.  308 


INDEX. 


597 


Succus  entericus,  digestive  action  of,  308 

ferments  of,  308 
Suction  action  of  the  heart,  134 
Sudorific  drugs,  2(50 
Suffocation  (see  Asphyxia). 
Sugar  injections,  lymphagogic  action  of,  73 
Sugars,  absorption  of,  313,  317 

consumption  of,  by  the  tissues,  353 

effect  of,  on  glycogen  formation,  328 

synthesis  of,  533 
Sulphates  of  the  urine,  estimation  of,  506 

origin  of,  506 
Sulph-hsemoglobin,  506 
Sulphur,  elimination  of,  340 

metabolism  of,  507 

neutral,  506 

occurrence  of,  505 
Sulphuretted  hydrogen,  inhalation  of,  440 

properties  of,  506 
Sulphuric  acid,  506 
Sulphurous  acid,  506 

Superior  laryngeal  nerves,  influence  of,  on  res- 
piration, 459,  462 
Supplemental  air,  definition  of,  427 
Suprarenal  capsules,  extirpation  of,  271 
Swallowing,  375 
Sweat,  amount  of,  258,  342 

composition  of,  259,  342 

nitrogenous  constituents  of,  512 
Sweat-centres,  spinal,  261 
Sweat-glands,  secretory  nerves  of,  259 
stimulation  of,  260 
structure  of,  258 
Sweat-nerves,  259 

Sweat-secretion,  action  of  drugs  on,  260 
Sympathetic  nerves,  cardiac,  168,  171 
pulmonary,  466 
reflex  influence  of,  on  the  pulse-rate,  175 

secretory  fibres  to  the  pancreas,  232 
to  the  salivary  glands,  218,  222 

vaso-motor  centres,  200 
Synthesis  of  proteids,  518,  582 

of  sugars,  563 
Synthetic  processes  of  plants,  518 
Syntonin,  absorption  of,  315 

occurrence  of,  in  peptic  digestion,  292 
Systole,  auricular,  124,  136 

ventricular,  123 

Tartar,  524 

Taurin,  507,  543 

Tea,  nutritive  value  of,  357 

Temperature,  axillary,  468 

body-,  effect  of,  on  respiratory  activity,  432 
influence  of  drags  on,  472 
lowering  of,  472 
variations  of,  469 
effect  of,  on  enzymes,  281 
on  beat  dissipation,  487 
on  metabolism,  362 
on  sweat  glands,  260 
on  tin-  respiratory  quotient,  438 
on  tryptic  digest  ion,  301 
external,  effect  of,  on  respiration,  426 
on   respiratory  exchanges,  432 
on  thermotaxis,  196 
influence  of,  on  beat  production,  483 
on  ptyalin,  286 
of  annuals,  167 
of  respired  air,  I  in 
post-mortem  rise  of,  497 
regulat  ion  of,  473 
topography  of.  468 
Temporal  muscle,  :'>7'.' 
Tension  of  the  blood-gases,  415 
Testicular  extracts,  action  of,  273 
Testis,  internal  secretion  of,  273 


Tetanus  of  the  heart,  165 
Tetramethylene-diamin,  543 
Theobromin,  553 
Theophyllin,  553 
Thermo-accelerator  centres,  492 
Thermogeuesis,  477 

mechanism  of,  489 
Thermogenic  centres,  491 
nerves,   190 
tissues,  490 
Therino-inhibitory  centres,  492 
Thermolysis,  485 

mechanism  of,  494 
Thermotaxis,  489,  495,  496 
Thiolactic  acid,  547 
Thiry-Vella  fistula,  308 
Thoracic  duct,  145 
Thorax,  effects  of  opening  the,  115 
movements  of,  in  respiration,  397 
negative  pressure  in  the,  396 
Thrombin,  58,  280 
Thrombus,  60 
Thymic  acid,  579 
Thyroglobuliu,  509 
Thyroidectomy,  269 
Tbyroid  extract,  injection  of,  269,  270 
Thyroids,  anatomy  of,  267 
extirpation  of,  268 
functions  of,  268 
grafting  of,  269 
internal  secretion  of,  270 
Thyroiodine,  50!) 
Tidal  air,  volume  of,  426 
Time  of  a  complete  circulation,  79 
Tinctures,  definition  of,  535 
Tissue-proteid,  definition  of,  346 
Tissue-respiration,  422 
Tongue,  vaso-motor  nerves  of,  204 
Tonicity  of  involuntary  muscle,  371 

of  vaso-constrictor  centre.  199 
Tonograph,  definition  of,  127 
Tonometer,  188 
Tonus,  ventricular,  during  vagus  stimulation, 

163 
Transfusion  of  blood,  61 
Transversalis    abdominis    muscle,    respiratory 

action  of,  |i>7 
Trapezius  muscle,  respiratory  action  of,  405 
Traube-Hering  waves,  201 
Triangulares  sterni  muscles,  expiratory  action 

of,  407 
Trigeminal  nerves,  inlluence  of,  on   respiration, 

463 
Trimethylamine,  511 

Trioses,  559 

Trommel's  test  for  carbohydrates,  562 
Tropseolin  00  test  for  mineral  acid,  289 
Trophic  inlluence  of  the  vagi  on  the  heart,  167 

nerves  of  tin-  salivary  glands,  224 
pulmonary,  166 
Trypsin,  232 

effect  of.  on  blood  coagulation,  63 

exl  racts,  preparal  ion  of,  301 

properl  ies  of,  301 
Trypsinogen,  235 

granules,  235 
Tryptic  digestion,  products  of,  302 

value  of.  304 
Tryptophan,  57 1 
Tubules,  ii mi iferous,  250 
Tunicin,  566 

Ty  rosin,  570 

formation  of,  in  tryptic  digestion.  303 

I 'nits,  calorimel  ric,   177 

Unorganized  ferments,  definition  of,  279 

I  na.  amount  of,  in  sweat,  335 


598 


INDEX. 


Urea,  amount  of,  in  the  blood,  51 
in  the  urine,  335 
antecedents  of,  '■>"■'■> 
elimination  of,  252 
estimation  of,  .~>4!l 
formation  of,  after  removal  of  the  liver,  337 

in  the  liver,  331 
origin  of,  in  the  body,  550 

in  the  liver,  266 
preparation  of,  5  18 
from  proteid,  '-V.'u 
presence  of,  in  sweat,  342 
properties  of,  ~>1!' 
Ureters,  movements  of,  371,  389 
Uric  acid,  formation  of,  338 
in  the  liver,  322 
in  the  spleen,  333 
molecular  structure  of,  554 
occurrence  of,  338 
origin  <>t',  in  birds,  557 

in  mammals,  338,  556" 
preparation  of,  555 
properties  of,  555 
Urinary  bladder,  innervation  of,  392 
movements  of,  390 
pigments,  origin  of,  from  haemoglobin,  45 
secretion,  normal  stimulus  for,  255 

relation  of,  to  the  blood-flow  through  the 
kidney,  253 
Urine,  acidity  of,  after  meals,  290 
composition  of,  250,  334 

ethereal  sulphates  of,  572 

secretion  of,  251 
Uriniferons  tubules,  secretory  function  of,  252 

structure  of,  250 
Urobilin,  574 

VAGUS,  anabolic  action  of,  on  the  heart,  166 
anatomy  of,  in  the  dog,  159 
cardiac  branches  of,  159 
effect  on  the  heart,  nature  of,  166 
gastric  branches  of,  381 
inhibition,  dependence  of,  on  the   character 

of  the  stimulus,  165 
intestinal  branches  of,  385 
nerves,  pulmonary  branches  of,  465 
relation  of,  to  apnoea,  442 
respiratory  function  of,  459 
pneumonia.   4<ii> 
secretory  fibres  of,  to  the  pancreas,  232 

to  the  stomach,  239 
stimulation,  auricular  effects  of,  164 
effect  of,  on  the  heart,  152,  163 
on  the  ventricle,  162 
latent  period  of,  162 
Valsalva's  experiment,  452 

sinuses,  111 
Valves,  auriculo-ventricular,  108 
of  lymphatic  vessels,  146 
semilunar,  110 
Valvules  conniventes,  value  of,  in   absorption, 

314 
Vaseline,  531 

Vasoconstrictor  centre,  rhythmical  activity  of, 
201,  151 
nerves,  discovery  of,  193 
Vaso  dilator  nerves,  discovery  of,  194 
Vaso-motor  centre,  medullary,  198 
cent  res.  spinal.   199 

sympathetic,  200 

nerves,  anatomy  of,  198 

methods  of  investigating,  195 

of  the  brain,  203 

of  the  generative  organs,  208 

of  the  head.  204 

of  Che  heart.  206 

of  the  intestines,  206 


Vaso-motor  nerves  of  the  kidney,  207,  256 
of  the  limbs,  209 
of  the  liver,  206 
of  the  lungs,  205,  466 
of  the  muscles,  210 
of  the  pancreas,  207 
of  the  portal  system,  209 
of  the  salivary  glands,  222 
of  the  spleen,  2<>7 
of  the  tongue.  205 
of  the  veins,  195 
special  properties  of,  197 
reflexes,  201 
through  the  vagi,  172 
Vegetable  foods,  composition  of,  278 

proteids,  577 
Veins,  effeel  of  compression  of,  on  lymph  forma- 
tion. 72 
entrance  of  air  into,  97 
rate  of  How  in,  101 
vaso-motor  nerves  of,  209 
Velocity  of  blood-flow,  99,  100,  101 
Vense  Thebesii,  1S4 
Veno-motor  nerves  of  the  limbs,  209 
Venous  blood-How.  effect  of  the  auricles  on,  137 
circulation,  95,  96 
pressure,  91 ,  94 
pulse,  respiratory,  96 
Ventilation,  principles  of,  439 
Ventricles,  independent  rhvtbm  of,  152 

work  done  by,  106,  107 
Ventricular  cycle,  analysis  of,  133 
diastole,  duration  of,  123 
pressure-curves,  analysis  of,  128 
pressures,  125 
systole,  duration  of,  123 
Vernix  caseosa,  258 
Vessels  of  Thebesius,  186 
Villus,  intestinal,  structure  of,  318 
Viscero-motor  nerves  to  the  intestines,  385 
Viscosity  of  irrigating  media  for  the  heart,  191 
Visual  purple,  575 
Vital  capacity  of  the  lungs,  427 

force,  definition  of,  25 
Vitellin,  composition  of,  579 
Voluntary  control  of  the  heart,  178 
Vomiting.  387 
causes  of,  388 
centre  for,  389 
nervous  mechanism  of,  388 

Wandering  cells,  definition  of,  48 
Water,  absorption  of,  313,  318 

amount  lost  through  the  lungs,  410 

distribution  of,  503 

effect  of,  on  pancreatic  secretion,  236 

elimination  of,  340 

imbibition  of,  504 

latent  beat  of,  504 

nutritive  value  of,  276,  354 

properties  of,  503 
Wharton's  duct,  217 
William's  frog-heart  apparatus,188 

valve,  187 
Wines,  535 
Wirsung's  duct,  231 
Work  done  by  the  heart  ventricles,  106,  107 

Xanthin,  553 

physiological  significance  of,  339 
Xantho-protcid  reaction,  576 
Xylose,  562 

Yawning,  454 

Zymogen  granules,  definition  of,  228 
of  the  pancreas,  235 


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Edited  by  J.  M.  Baldy,  M.  1).,  Professor  of  Gynecology,  Philadelphia 
Polyclinic,  etc.  Handsome  imperial  octavo  volume  of  718  pages;  341 
illustrations  in  the  text,  and  38  colored  and  half-tone  plates.  Cloth, 
.-,(1.00  net;  Sheep  or  Half  Morocco,  $7.00  net.     Sold  by  Subscription. 

An  American  Text-Book  qf  Legal  Medicine  arid  Toxi- 
cology. 

Edited  by  Frederick  Peterson,  M.  D.,  Chief  of  Clinic,  Nervous 
Department,  College  of  Physicians  and  Surgeons,  New  York  ;  and 
Walter  S.  Haines,  M.D..  Professor  of  Chemistry,  Pharmacy,  and 
Toxicology,   Rush   Medical   College,  Chicago.      In  Preparation. 

An  American  Text-Book  qf  Obstetrics. 

Edited  by  Richard  C.  Norris,  M.  D.  ;  Art  Editor,  Robert  L.  Dick- 
inson, M.  I).  Handsome  imperial  octavo  volume  of  1014  pages; 
nearly  900  beautiful  colored  and  half-tone  illustrations.  Cloth,  $7.00 
net;   Sheep  or  Half  Morocco,  S8.00  net.     Sold  by  Subscription. 

An  American  Text-Book  qf  Pathology. 

Edited  by  Ludvig  Hektoen,  M.  D.,  Professor  of  Pathology  in  Rush 
Medical  College,  Chicago;  and  David  Riesman,  M.  D.,  Demonstrator 
of  Pathologic:  Histolo^v  in  the  University  of  Pennsylvania.  Imperial 
<>.  tavo,  over  1250  pages,  443  illustrations,  66  in  colors.    By  Subscription. 

An  American  Text-Book  qf  Physiology,     second  Edition. 

Revised,  in  Two  Volumes. 

Edited  by  William  H.  Howell,  Ph.D.,  M.  D.,  Professor  of  Physi- 
ology, Johns  Hopkins  University,  Baltimore,  Md.  Two  royal  octavo 
volumes  of  about  600  pages  each.  Fully  illustrated.  Per  volume: 
Cloth,  S3. 00  net;    Sheep  or  Half  Morocco,  S3. 75  net. 

An  American  Text- Book  qf  Surgery.    Third  Edition. 

Edited  U  William  W.  Keen,  M.  D.,  LL.  D.,  F.  R.  C.  S.  (Hon.) ;  and 
J.  William  White,  M.  1>..  Ph.  D.  Handsome  octavo  volume  of  1230 
pages;  496  wood-cuts  and  37  colored  and  half-tone  plates.  Thoroughly 
revised  and  enlarged,  with  a  section  devoted  to  "The  Use  of  the  Ront- 
gen  Rays  in  Surgery."  (doth,  $7.00  net;  Sheep  or  Half  Morocco, 
00  net. 


OF   IV.  B.  SAUNDERS   &    CO. 


GET  THE  BEST  THE  NEW  STANDARD 

The  American  Illustrated  Medical  Dictionary. 

Second  Edition,  Revised. 

For  Practitioners  and  Students.     A  Complete  Dictionary  of  the  Terms 

used  in  Medicine,  Surgery,  Dentistry,  Pharmacy,  Chemistry,  and  the 
kindred  branches,  including  much  collateral  information  of  an  encyclo- 
pedic character,  together  with  new  and  elaborate  tables  of  Arteries, 
Muscles,  Nerves,  Veins,  etc.  ;  of  Bacilli,  Bacteria,  Micrococci,  Strepto- 
cocci ;  Eponymic  Tables  of  Diseases,  Operations,  Signs  and  Symptoms, 
Stains,  Tests,  Methods  of  Treatment,  etc.,  etc.  B)  W.  A.  Newman 
Dorland,  A.M.,  M.  D.,  Editor  of  the  "American  Pocket  Medical 
Dictionary."  Handsome  large  octavo,  nearly  800  pages,  bound  in 
full  flexible  leather.     Price,  $4.50  net;   with  thumb  index,  $5.00  net. 

Gives  a  Maximum  Amount  of   Matter   in   a    Minimum    Space    and    at   the  Lowest 

Possible  Cost. 

This  Edition  contains  all  the  Latest  Words. 

"  I  must  acknowledge  my  astonishment  at  seeing  how  much  he  has  condensed  within 
relatively  small  space.  I  find  nothing  to  criticise,  very  much  to  commend,  and  was  interested 
in  finding  some  of  the  new  words  which  are  not  in  other  recent  dictionaries. "— R<  (SWELL  PARK, 
Professor  of  Principles  and  Practice  of  Surgery  and  Clinical  Surgery,  University  of  Buffalo. 

"  I  congratulate  you  upon  giving  to  the  profession  a  dictionary  so  compact  in  its  structure, 
and  so  replete  with  information  required  by  the  busy  practitioner  and  student.    It  is  a  nee 
as  well  as  an  informed  companion  to  every  doctor.     It  should  be  upon  the  desk  of  every  prac- 
titioner and  student  of  medicine." — JOHN    B.   MURPHY,  Professor  of  Surgery  and   Clinical 
Surgery,  Northwestern   University  Medical  School,  Chicago. 

The  American  Pocket  Medical  Dictionary.    Thi*d  Edi*on- 

Revised. 

Edited  by  W.  A.  Newman  Dorland,  M.  1).,  Assistant  Obstetrician  to 
the  Hospital  of  the  University  of  Pennsylvania;  Fellow  of  the  Amer- 
ican Academy  of  Medicine.  Containing  the  pronunciation  and  defini- 
tion of  the  principal  words  used  in  medicine  and  kindred  sciences,  with 
64  extensive  tables.  Handsomely  bound  in  flexible  leather,  with  gold 
edges.     Price  Si-oo  net;   with  thumb  index,  $1.25  net. 

The  American  Year-Book  of  Medicine  and  Surgery. 

A  Yearly  Digest  of  Scientific  Progress  and  Authoritative  Opinion  in  all 
branches  of  Medicine  and  Surgery,  drawn  from  journals,  monographs, 
and  text-books  of  the  leading  American  and  foreign  authors  and  investi- 
gators. Arranged  with  critical  editorial  comments,  by  eminent  Amer- 
ican specialists,  under  the  editorial  charge  of  George  Si.  Got  LD,  M.  1  >. 
Year-Book  of  1901  in  two  volumes — Vol.  I.  including  General  Medicine; 
Vol.  II.,  General  Surgery.  Per  volume:  Cloth,  S3. 00  net;  Half  Mo- 
rocco, $3.75  net.     Sold  by  Subscription. 

Abbott  on  Transmissible  Diseases,    second  Edition.  Revised. 

The  Hygiene  of  Transmissible  Disease's:  their  Causation,  Modes  of 
Dissemination,  and  Methods  of  Prevention.  By  A.  ('.  Abbott,  M.  D., 
Professor  of  Hygiene  and  Bacteriology,  University  of  Pennsylvania. 
Octavo,  351    pages,  with   numerous  illustrations.      Cloth,  $2.50  net. 


MEDICAL   Pi TBLLCA  TIONS 


Anders*  Practice  of  Medicine.       Fifth  Revised  Edition. 

A  Text-Book  of  the  Practice  of  Medicine.  By  James  M.  Anders, 
M.  D..  I'll.  1>.,  1. 1..  I)..  Professor  of  the  Practice  of  Medicine  and  of 
Clinical  Medicine.  Medico-Chirurgical  College,  Philadelphia.  Hand- 
some octavo  volume  of  1292  pages,  fully  illustrated.  Cloth,  $5.50  net; 
Sheep  or  Half  Morocco,  56.50  net. 

Bastin's  Botany. 

Laboratory  Exercises  in  Botany.  By  Edson  S.  Bastin,  M.  A.,  late 
I'rofosor  of  Materia  Medica  and  Botany,  Philadelphia  College  of 
Pharmacy.     Octavo,  536  pages,  with  87  plates.     Cloth,  $2.00  net. 

Beck  on  Fractures. 

Fractures.  By  Carl  Beck,  M.  ]).,  Surgeon  to  St.  Mark's  Hospital  and 
the  New  York  German  Poliklinik,  etc.  With  an  appendix  on  the  Prac- 
tical  Use  of  the  Rontgen  Rays.  335  pages,  170  illustrations.  Cloth, 
$3.50  net. 

Beck's  Surgical  Asepsis. 

A  Manual  of  Surgical  Asepsis.  By  Carl  Beck,  M.  D.,  Surgeon  to  St. 
Mark's  Hospital  and  the  New  York  German  Poliklinik,  etc.  306  pages; 
65  text-illustrations  and  12  full-page  plates.     Cloth,  $1.25  net. 

Bergey's  Principles  of  Hygiene. 

The  Principles  of  Hygiene:    A    Practical  Manual  for   Students,  Physi- 
cians, and  Health   Officers.      By    D.    H.    Bergey,   A.M.,    M.  D.,    First 
Assistant,  Laboratory  of  Hygiene,  University  of  Pennsylvania.     Hand 
some  octavo  volume  of  495  pages,  illustrated.     Cloth,  53.00  net. 

Boisliniere's    Obstetric   Accidents,   Emergencies,   and 
Operations. 

Obstetric  Accidents,   Emergencies,  and  Operations.     By  L.  Ch.  Bois 
uniere,  M.  D.,  late  Emeritus  Professor  of  Obstetrics,  St.  Louis  Medical 
Coflege.      381  pages,  handsomely  illustrated.      Cloth.  $2.00  net. 

Bohm,  Davidoff,   arid  Huber's  Histology. 

A  Text-Book  of  Human  Histology.  Including  Microscopic  Technic. 
B3  Dr.  A.  A.  Bohm  and  Dr.  M.  von  Davidoff,  of  Munich,  and 
G.  Car]  Huber,  M.  D.,  Junior  Professor  of  Anatomy  and  Director  of 
Histological  Laboratory,  University  of  Michigan.  Handsome  octavo 
of  503  pages,  with  351  beautiful  original  illustrations.     Cloth,  $3.50  net. 

Butler's  Materia  Medica,  Therapeutics,  arid  Pharma- 
cology.     Third  Edition,  Revised. 

A  Text-Book  of  Materia  Medica,  Therapeutics,  and  Pharmacology. 
By  George  F.  Butler,  Ph.  ('•.,  M.  D.,  Professor  of  Materia  Medica  and 
of  Clinical  Medicine,  College  of  Physicians  and  Surgeons.  Chicago. 
Octavo,  874  pages,  illustrated.  Cloth,  $4.00  net;  Sheep  or  Half  Mo- 
rocco, S5.00  net. 


OF   IV.  B.  SAUNDERS   &>    CO. 


Chapin  on  Insanity. 

A  Compendium  of  Insanity.  By  John  B.  Chapin,  M.  D.,  LL.  D., 
Physician-in-Chief,  Pennsylvania  Hospital  for  the  Insane:  Honorary 
Member  of  the  Medico-Psychological  Society  of  Creat  Britain,  of  the 
Society  of  Mental  Medicine  of  Belgium,  etc.  121110,  234  pages,  illus- 
trated.    Cloth,  $i. 25  net. 

Chapman's   Medical    Jurisprudence  arid  Toxicology. 

Second  Edition,  Revised. 

Medical  Jurisprudence  and  Toxicology.  By  Henry  C.  Chapman, 
M.  D.,  Professor  of  Institutes  of  Medicine  and  Medical  Jurisprudence, 
Jefferson  Medical  College  of  Philadelphia.  254  pages,  with  55  illus- 
trations and  3  full-page  plates  in  colors.     Cloth,  Si  50  net. 

Church  and  Peterson's  Nervous  arid  Mental  Diseases. 

Third  Edition,  Revised  and  Enlarged. 

Nervous  and  Mental  Diseases.  By  Archibald  Church,  M.  IV.  Pro- 
fessor of  Nervous  and  Mental  Diseases,  and  Head  of  the  Neurological 
Department,  Northwestern  University  Medical  School,  Chicago;  and 
Frederick  Peterson,  M.  D.,  Chief  of  Clinic.  Nervous  Department, 
College  of  Physicians  and  Surgeons,  New  York.  Handsome  octavo 
volume  of  875  pages,  profusely  illustrated.  Cloth,  $5.00  net;  Sheep  or 
Half  Morocco,  $6. 00  net. 

Clarkson's  Histology. 

A  Text-Book  of  Histology,  Descriptive  and  Practical.  By  Arthur 
Clarkson,  M.  B. ,  CM.  Edin.,  formerly  Demonstrator  of  Physiology 
in  the  Owen's  College,  Manchester;  late  Demonstrator  of  Physiology 
in  Yorkshire  College,  Leeds.  Large  octavo,  554  pages;  22  engravings 
and  174  beautifully  colored  original  illustrations.      Cloth,  54.00  net. 

Corwin's  Physical  Diagnosis.     Third  Edition.  Revised. 

Essentials  of  Physical  Diagnosis  of  the  Thorax.  By  Arthur  M. 
Corwix,    A.M.,    M.  D.,    Instructor    in     Physical     Diagnosis    in    Rush 

Medical  College,  Chicago.     219  pages,  illustrated.     Cloth.  51.25   net. 

DaCoSta'S    Surgery.       Third  Edition,  Revised. 

Modern  Surgery,  General  and  Operative.  By  John  Chalmers  Da 
Costa,  M.  D.,  Professor  of  Principles  of  Surgery  and  Clinical  Surgery, 
Jefferson  Medical  College,  Philadelphia  ;  Surgeon  to  the  Philadelphia 
Hospital,   etc.       Handsome   octavo  volume    of    1117    pages,   profusely 

illustrated.     Cloth,  $5.00  net;   Sheep  or  Half  Morocco,  50.00   net. 

Enlarged  by  over  200  Pages,  with  more  than   100  New  Illustrations. 

Davis's  Obstetric  Nursing. 

Obstetric  and  Gynecologic  Nursing.  B)  Edward  P.  Davis,  A.M.. 
M.  1).,  Professor  of  Obstetrics,  Jefferson  Medical  College  and  Phila- 
delphia Polyclinic;  Obstetrician  and  Gynecologist,  Philadelphia  Hos- 
pital.    121110,  400  pages,  illustrated.     Crushed  Buckram,  s  1  -  75  net. 


MEDICAL   PU/:/./( '.  /  TIONS 


DeSchweinitz  on  Diseases  of  the  Eye.   Third  Edition,  Revised. 

Diseases  of  the  Eve.  A  Handbook  of  Ophthalmic  Practice.  By  ('.. 
E.  de  Schweinitz,  M.  D.,  Professor  of  Ophthalmology,  Jefferson  Medi- 
cal  College,  Philadelphia,  etc.  Handsome  royal  octavo  volume  of  696 
pages  :  256  fine  illustrations  and  2  chromo-lithographic  plates.  Cloth, 
S4.00  net;   Sheep  or  Half  Morocco,  $5.00  net. 

Dorland's  Dictionaries. 

[See  American  Illustrated  Medical  Dictionary  and  American 

Pocket  Medical  Dictionary  on  page  3.] 

Dofland'S    Obstetrics.       Second  Edition,  Revised  and  Greatly  Enlarged. 

Modern  Obstetrics.  By  W.  A.  Newman  Dorland,  M.  D.,  Assistant 
Demonstrator  of  Obstetrics,  University  of  Pennsylvania ;  Associate  in 
Gynecology,  Philadelphia  Polyclinic.  Octavo  volume  of  797  pages, 
with  201   illustrations.     Cloth,  £4.00  net. 

Eichhorst's  Practice  of   Medicine. 

A  Text-Book  of  the  Practice  of  Medicine.  By  Dr.  Herman  ElCHHORST, 
Professor  of  Special  Pathology  and  Therapeutics  and  Director  of  the 
Medical  Clinic,  University  of  Zurich.  Translated  and  edited  by  Augus- 
tus A.   Eshner,   M.  D.,   Professor   of   Clinical    Medicine,    Philadelphia 

Polyclinic.    Two  octavo  volumes  of  600  pages  each,  over  150  illustrations. 

Prices  per  set :   Cloth,  $6.00  net ;   Sheep  or  Half  Morocco,  $7.50  net. 

Friedrich  arid  Curtis  on  the  Nose,  Throat,  arid  Ear. 

Rhinology,  Laryngology,  and' Otology,  and  Their  Significance  in  Gen- 
eral Medicine.  By  Dr.  E.  P.  Friedrich,  of  Leipzig.  Edited  by  H. 
HOLBROOK  CURTIS,  M.  D.,  Consulting  Surgeon  to  the  New  York  Nose 
and  Throat  Hospital.     Octavo,  348  pages.     Cloth,  $2.50  net. 

Frothingham's  Guide  for  the  Bacteriologist. 

Laboratory  Guide  for  the  Bacteriologist.  By  Langdon  Frothingham, 
M.  I).  V.,  Assistant  in  Bacteriology  and  Veterinary  Science,  Sheffield 
Scientific  School,  Yale  L'niversity.     Illustrated.      Cloth,  75  cts.  net. 

Garrigues'  Diseases  of  Women.     Third  Edition,  Revised. 

Diseases  of  Women.  By  Henry  J.  Garrigues,  A.M.,  M.  D.,  Gyne- 
cologist to  St.  Mark's  Hospital  and  to  the  German  Dispensary,  New- 
York  City.  Octavo,  756  pages,  with  367  engravings  and  colored  plates. 
Cloth,  $4.50  net;  Sheep  or  Half  Morocco,  $5.50  net. 

Gorham's  Bacteriology. 

A  Laboratory  Course  in  Bacteriology.  By  F.  P.  GoRHAM,  M.  A., 
Assistant  Professor  in  Biology,  Brown  University.  121110  volume  of 
192   pages,  97  illustrations.      Cloth,  $1.25   net. 


OF    IV.  B.  SAUNDERS   6-    CO. 


Gould  arid  Pyle's  Curiosities  of   Medicine. 

Anomalies  and  Curiosities  of  Medicine.  By  George  M.  Gould,  M.D., 
and  Walter  L.  Pyle,  M.  I .).  An  encyclopedic  collection  of  rare  and 
extraordinary  cases  and  of  the  most  striking  instances  of  abnormality  in 
all  branches  of  Medicine  and  Surgery,  derived  from  an  exhaustive 
research  of  medical  literature  from  its  origin  to  the  present  day 
abstracted,  classified,  annotated,  and  indexed.  Handsome  o< 
volume  of  968  pages;  295  engravings  and  12  full-page  plates.  Popular 
Edition.      Cloth,  S3-00  net;  Sheep  or  Half  Morocco,  S4.00  net. 

Grafstrom's  Mechano-Therapy. 

A  Text-Book  of  Mechano-Therapy  (Massage  and  Medical  Gymnastics). 
By  Axel  V.  Grafstrom,  B.  Sc,  M.  D.,  late  House  Physician,  City  Hos- 
pital, Blackwell's  Island,  New  York.  i2mo,  139  pages,  illustrated. 
Cloth,  £1.00  net. 

Griffith    OI1    the    Baby.       Second  Edition,  Revised. 

The  Care  of  the  Baby.  By  J.  P.  Crozer  Griffith,  M.  D.,  Clinical 
Professor  of  Diseases  of  Children,  University  of  Pennsylvania ;  Phy- 
sician to  the  Children's  Hospital,  Philadelphia,  etc.  121110,  404  pages; 
67  illustrations  and  5  plates.     Cloth,  $1.50  net. 

Griffith's  Weight  Chart. 

Infant's  Weight  Chart.  '  Designed  by  J.  P.  Crozer  Griffith,  M.  D., 
Clinical  Professor  of  Diseases  of  Children,  University  of  Pennsylvania. 
25  charts  in  each  pad.     Per  pad,   50  cts.  net. 

Hart's  Diet  in  Sickness  arid  in  Health. 

Diet  in  Sickness  and  Health.  By  Mrs.  Ernest  Hart,  formerly  Student 
of  the  Faculty  of  Medicine  of  Paris  and  of  the  London  School  of  Medi- 
cine for  Women;  with  an  Introduction  by  Sir  Henry  Thompson, 
F.  R.  C.  S.,  M.  D.,  London.      220  pages.     Cloth.  $1.50  net. 

Haynes'  Anatomy. 

A  Manual  of  Anatomy.     By  Irving  S.  Haynes,   M.  D.,  Professor  of 
Practical  Anatomy  in  Cornell  University  Medical  College.     680  pa. 
42  diagrams  and  134  full-page  half-tone  illustrations  from  original  photo- 
graphs of  the  author's  dissections.      Cloth,  $2.50  net. 

Heisler'S    Embryology.        Second  Edition.  Revised. 

A  Text-Book  of  Embryology.  By  John  ('.  Heisler,  M.  IV,  Professor 
of  Anatomy,  Medico-Chirurgical  College,  Philadelphia.    Octavo  volume 

of  405  pages,  handsomely  illustrated.      Cloth.  $2.50  net. 

Hirst'S    Obstetrics.       Third  Edition,  Revised  and  Enlarged. 

A  Text-Book  of  Obstetrics.  By  Barton  (  Iooki  Hirst,  M.  I).,  Professor 
of  Obstetrics,  University  of  Pennsylvania.  Handsome  octavo  volume 
of  873  pages  ;  704  illustrations,  36  of  them  in  colors.  Cloth,  S5.00  net; 
Sheep  or  Half  Morocco,  $6. 00  net. 


ME  DICAL   PUBLICA  TIONS 


Hyde  arid  Montgomery  on   Syphilis  arid  the  Venereal 

Diseases.       Second  Edition,  Revised  and  Greatly  Enlarged. 

Syphilis  and  the  Venereal  Diseases.  By  James  Nevins  Hyde,  M.  D., 
Professor  of  Skin  and  Venereal  Diseases,  and  Frank  H.  Montgomery, 
M.  1).,  Associate  Professor  of  Skin,  Genito-Urinary,  and  Venereal  Dis- 
eases in  Rush  Medical  College,  Chicago,  111.  Octavo,  594  pages, 
profusely  illustrated.      Cloth,  S4.00  net. 

The  International  Text- Book  of  Surgery.     in  Two  volumes. 

Bv  American  and  British  Authors.  Edited  by  ].  Collins  Warren, 
M.  I)..  LI,.  I).,  F.  R.  C.  S.  (Hon.),  Professor  of  Surgery,  Harvard  Medi- 
cal School,  Poston  ;  and  A.  PEARCE  Gould,  M.  S.,  F.  R.  C.  S.,  Lecturer 
on  Practical  Surgery  and  Teacher  of  Operative  Surgery.  Middlesex 
Hospital  Medical  School,  London,  Eng.  Vol.  I.  General  Surgery. — 
Handsome  octavo,  947  pages,  with  458  beautiful  illustrations  and  9 
lithographic  plates.  Vol.  II.  Special  or  Regional  Surgery. — Handsome 
octavo,  1072  pages,  with  471  beautiful  illustrations  and  8  lithographic 
plates.  Sold  by  Subscription.  Prices  per  volume:  Cloth,  $5.00  net; 
Sheep  or  Half  Morocco,  $6. 00  net. 

"  It  is  the  most  valuable  work  on  the  subject  that  has  appeared  in  some  years.  The  clini- 
cian and  the  pathologist  have  joined  hands  in  its  production,  and  the  result  must  be  a  satis- 
faction to  the  editors  as  it  is  a  gratification  to  the   conscientious  reader." — Annals  of  Surgery. 

"  This  is  a  work  which  comes  to  us  on  its  own  intrinsic  merits.  Of  the  latter  it  has  very 
ts  i^  excellent,  and  their  treatment  by  the  different  authors 
is  equally  so.     \Y!.  cially  to  be  recommended  is  the  painstaking  endeavor  of  each 

writer  to  make  his  subject  clear  and  to  the  point.  To  this  end  particularly  is  the  technique 
of  operations  lucidly  described  in  all  necessary  detail.  And  withal  the  work  is  up  to  date  in 
a  very  remarkable  di  iny  of  the  latest  operations  in  the  different  regional  parts  of  the 

body  being  given  in  full  details.  There  is  not  a  chapter  in  the  work  from  which  the  reader 
may  not  learn  something  new."  —  Medical  Record,  New  York. 

Jackson's  Diseases  of  the  Eye. 

A  Manual  of  Diseases  of  the  Eye.  By  Edward  Jackson,  A.  M.,  M.  D., 
Emeritus  Professor  of  Diseases  of  the  Eye,  Philadelphia  Polyclinic  and 
College  for  (Graduates  in  Medicine.  121110  volume  of  535  pages,  with 
178  illustrations,  mostly  from  drawings  by  the  author.     Cloth,  $2.50  net. 

Keating's  Life  Insurance. 

How  to  Examine  for  Life  Insurance.  By  '  n\  M.  Kkating,  M.  D., 
Fellow  of  the  College  of  Physicians  of  Philadelphia  ;  Ex-President  of  the 
Association  of  Life  Insurance  Medical  Directors.  Royal  octavo,  211 
pages.     With  numerous  illustrations.     Cloth,  S2.00  net. 

Keen  on  the  Surgery  of  Typhoid  Fever. 

The  Surgical  Complications  and  Sequels  of  Typhoid  Fever.  By  Wm. 
W.  Kit  :n.  M.  1)..  LL.  I).,  F.  R.  C.  S.  (Hon.),  Professor  of  the  Principles 
of  Surgery  and  of  Clinical  Surgery,  Jefferson  Medical  College,  Phila- 
delphia, etc.    Octavo  volume  of  386  pages,  illustrated.    Cloth,  $3.00  net. 

Keen's    Operation    Blank.       Second  Edition,  Revised  Form. 

An  Operation  Blank,  with  Lists  of  Instruments,  etc.,  Required  in  Vari- 
ous Operations.  Prepared  by  W.  W.  Keen,  M.  D.,  LL.  D.,  F.  R.  C.  S. 
(Hon.),  Professor  of  the  Principles  of  Surgery  and  of  Clinical  Surgery, 
Jefferson  Medical  College,  Philadelphia.  Price  per  pad,  blanks  for  fifty 
operations,  50  cts.  net. 


OF   IV.  B.  SAUNDERS   &    CO. 


Kyle  on  the  Nose  and  Throat,     second  Edition. 

Diseases  of  the  Nose  and  Throat.  By  D.  Braden  Kyle,  M.  D.,  Clinical 
Professor  of  Laryngology  and  Rhinology,  Jefferson  Medical  College, 
Philadelphia.  Octavo,  646  pages;  over  150  illustrations  and  6  litho- 
graphic plates.     Cloth,  $4.00  net;  Sheep  or  Half  Morocco,  $5.00  net. 

Laine's  Temperature  Chart. 

By  D.  T.  Laine,  M.  D.  For  recording  Temperature,  with  columns  for 
daily  amounts  of  Urinary  and  Fecal  Excretions,  Food,  etc.  ;  with  the 
Brand  Treatment  of  Typhoid  Fever  on  the  back  of  each  chart.  Pad  of 
25  charts,  50  cts.  net. 

Levy,  Klemperer,  arid  Eshner's  Clinical  Bacteriology. 

The  Elements  of  Clinical  Bacteriology.  By  Dr.  Ernst  Levy,  Pro- 
fessor in  the  University  of  Strasburg,  and  Felix  Klemperer,  Privat- 
docent  in  the  University  of  Strasburg.  Translated  and  edited  by 
Augustus  A.  Eshner,  M.  D.,  Professor" of  Clinical  Medicine,  Philadel- 
phia Polyclinic.     Octavo,  440  pages,  fully  illustrated.     Cloth,  $2.50  net. 

Lockwood's  Practice  of  Medicine.         Rev^^S^ed 

A  Manual  of  the  Practice  of  Medicine.  By  George  Roe  Lockwood, 
M.  D.,  Attending  Physician  to  Bellevue  Hospital.  New  York.  Octavo, 
847  pages,  illustrated,  including  22  colored  plates.      Cloth,  S4.00  net. 

Long's  Syllabus  of  Gynecology. 

A  Syllabus  of  Gynecology,  arranged  in  Conformity  with  "An  American 
Text-Book  of  Gynecology."  By  J.  W.  Long,  M.  D.,  Professor  of  Dis- 
eases of  Women  and  Children,  Medical  College  of  Virginia,  etc.  Cloth, 
interleaved,  $1.00  net. 

Macdonald's  Surgical  Diagnosis  and  Treatment. 

Surgical  Diagnosis  and  Treatment.  By  J.  W.  Macdonald,  M.  D. 
Edin.,  F.  R.  C.  S.  Edin.,  Professor  of  Practice  of  Surgery  and  (  liuical 
Surgery,  Hamline  University.  Handsome  octavo,  800  pages,  fully  illus- 
trated.    Cloth,  $5.00  net;  Sheep  or  Half  Morocco,  $6.00  net. 

Mallory  arid  Wright's  Pathological  Technique. 

Second  Edition,  Revised. 
Pathological  Technique.  A  Practical  Manual  for  Laboratory  Work  in 
Pathologv,  Bacteriology,  and  Morbid  Anatomy,  with  chapters  on  Post- 
Mortem  Technique  and  the  Performance  of  Autopsies.  By  Frank  B. 
Mallory,  A.M.,  M.  I).,  Assistant  Professor  of  Pathology,  Harvard 
University  Medical  School,  boston:  and  James  II.  Wright,  A.M.. 
M.  I).,  Instructor  in  Pathologv.  Harvard  University  Medical  School, 
boston.     Octavo,  432  pages,  fully  illustrated.     Cloth,  $ 3. 00  net. 

McClellan's  Anatomy  in  its  Relation  to  Art. 

Anatomy  in  its  Relation  to  Art.  An  Exposition  of  the  bom--  and 
Muscles  of  the  Human  Body,  with  Reference  to  their  Influence  upon 
its  Actions  and  External  form.  By  George  McClellan,  M.D.. 
Professor  of  Anatomy,  Pennsylvania  Academy  of  Fine  Arts.  Hand 
some  quarto  volume,  9  by  n1  .  inches.  Illustrated  with  338  original 
drawings  and  photographs;  260  pages  of  text.  Dark  Blue  Vellum, 
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McClellan's  Regional  Anatomy. 

Regional  Anatomy  in  its  Relations  to  Medicine  and  Surgery.  B) 
GEORGl  M<  Clei  LAN,  M.  I).,  Professor  of  Anatomy.  Pennsylvania  Acad- 
erm  of  line  Arts.  Two  handsome  quarto  volumes,  S84  pages  of  text, 
and  97  full-page  chromo-lithographic  plates,  reproducing  the  author's 
original  dissections.     Cloth.  $12.00  net;  Half  Russia,  $15.00  net. 

McFarland's  Pathogenic  Bacteria.    T^e  f/ovTr  ioo'ptyes.1" 

Text-Book  upon  the  Pathogenic  Bacteria.  By  Joseph  McFarland, 
M.  D.,   Professor  of  Pathology   and    Bacteriology,   Medico-Chirurgical 

College  of  Philadelphia,  etc.  Octavo  volume  of  621  pages,  finely 
illustrated.      Cloth,  S3. 25    net. 

Meigs  on  Feeding  in  Infancy. 

Feeding  in  Early  Infancy.  By  Arthur  V.  Meigs,  M.  D.  Bound  in 
limp  cloth,  flush  edges,  25  cts.  net. 

Moore's  Orthopedic  Surgery. 

A  Manual  of  Orthopedic  Surgery.  By  JAMES  E.  Moore,  M.  D.,  Pro- 
fessor  oi  < hthopedies  and  Adjunct  Professor  of  Clinical  Surgery,  Uni- 
versity of  Minnesota,  College  of  Medicine  and  Surgery.  Octavo  volume 
of  356  pages,  handsomely  illustrated.     Cloth,  $2.50  net. 

Morten's  Nurses'  Dictionary. 

Nurses'  Dictionary  of  Medical  Terms  and  Nursing  Treatment.  Con- 
taining Definitions  of  the  Principal  Medical  and  Nursing  Terms  and 
Abbreviations;  of  the  Instruments,  Drugs,  Diseases,  Accidents,  Treat- 
ments, Operations,  Foods,  Appliances,  etc.  encountered  in  the  ward  or 
in  the  sick-room.  By  Honnor  Morten,  author  of  "How  to  Become 
a  Nurse,"  etc.      161110,  140  pages.     Cloth,  $1.00  net. 

Nancrede's  Anatomy  and  Dissection.    Fourth  Edition. 

K>sentials  of  Anatomy  and  Manual  of  Practical  Dissection.  By  Charles 
B.  NANCR]  m  .  M.  D.,  Id,.  I).,  Professor  of  Surgery  and  of  Clinical  Sur- 
gery, University  of  Michigan,  Ann  Arbor.  Post-octavo,  500  pages,  with 
full-page  lithographic  plates  in  colors  and  nearly  200  illustrations.  Extra 
Cloth  (or  ( )ilc  loth  for  dissection-room),  $2.00  net. 

Nancrede's  Principles  of   Surgery. 

Lectures  on  the  Principles  of  Surgery.  By  Chas.  P..  Nancrede,  M.  D., 
LL.  D.,  Professor  of  Surgery  and  of  Clinical  Surgery,  University  of 
Michigan,  Ann  Arbor.   Octavo,  398  pages,  illustrated.    Cloth,  $2.50  net. 

Norris's  Syllabus  of  Obstetrics.    Third  Edition.  Revised. 

Syllabus  of  Obstetrical  Lectures  in  the  Medical  Department  of  the 
Universitv  of  Pennsylvania.  By  RlCHARD  C.  Norris,  A.M.,  M.  D., 
Instructor  in  Obstetrics  and  Lecturer  on  Clinical  and  Operative  Obstet- 
rics, University  of  Pennsylvania.  Crown  octavo,  222  pages.  Cloth, 
interleaved  for  notes,  $2.00  net. 


OF    IV.  B.  SAUNDERS   fir*    CO. 


Ogden  on  the  Urine. 

Clinical  Examination  of  the  Urine  and  Urinary  Diagnosis.  A  Clinical 
Guide  for  the  Use  of  Practitioners  and  Student-  of  Medicine  and  Sur- 
gery. By  ].  Bergen  Ogden,  M.  D.,  Instructor  in  Chemistry,  Harvard 
Medical  School.  Handsome  octavo.  416  pages,  with  54  illustrations 
and  a  number  of  colored  plates.     Cloth.  $3.00  net. 

Penrose's  Diseases  of  Women.    Fourth  Edition,  Revised. 

A  Text-Book  of  Diseases  of  Women.  By  Charles  B.  Penrose,  M.  D., 
Ph.D.,  formerly  Professor  of  Gynecology  in  the  University  of  Penn- 
sylvania.    Octavo  volume  of  538  pages,  handsomely  illustrated.     Cloth, 

$3-75  net- 

Pryor — Pelvic  Inflammations. 

The  Treatment  of  Pelvic  Inflammations  through  the  Vagina.  By  W. 
R.  Pryor,  M.  D.,  Professor  of  Gynecology,  New  York  Polyclinic. 
i2mo,  248  pages,  handsomely  illustrated.     Cloth,  $2.00  net. 

Pye's  Bandaging. 

Elementary  Bandaging  and  Surgical  Dressing.  With  Directions  con- 
cerning the  Immediate  Treatment  of  Cases  of  Emergency.  By  Walter 
Pye,  F.  R.  C.  S.,  late  Surgeon  to  St.  Mary's  Hospital,  London.  Small 
121110,  over  80  illustrations.     Cloth,  flexible  covers,  75  cts.  net. 

Pyle's  Personal  Hygiene. 

A  Manual  of  Personal  Hygiene.  Proper  Living  upon  a  Physiologic 
Basis.  Edited  by  Walter  L.  Pyle,  M.  D.,  Assistant  Surgeon  to  the 
Wills  Eye  Hospital,  Philadelphia.  Octavo  volume  of  344  pages,  fully 
illustrated.     Cloth,  $1.50  net. 

t*  J»       rkt_        *^1^v-.  Second  Edition,  Entirely 

Raymond  S    PhySlOlOgy.        Rewritten  and  Greatly  Enlarged. 

A  Text-Book  of  Physiology.     By  Joseph  II.  Raymond,  A.  M.,  M.  D., 

Professor  of  Physiolqgy  and  Hygiene  in  the  long  Island  College 
Hospital,  and  Director' of  Physiology  in  Hoagland  Laboratory,  New- 
York.     Octavo,  668  pages,  443  illustrations.     Cloth,  £3.50  net. 

Salinger  and  Kalteyer's  Modern  Medicine. 

Modern  Medicine.  By  Julius  L.  Salinger,  M.  D..  Demonstrator  of 
Clinical  Medicine,  Jefferson  Medical  College;  and  F.  J.  Kalteyer, 
M.D.,  Assistant  Demonstrator  of  Clinical  Medicine.  Jefferson  Medical 
College.      Handsome  octavo,  801  pages,  illustrated.      Cloth.  $4.00  net. 

Saundby's  Renal  and  Urinary  Diseases. 

Lectures  on  Renal  and  Urinary  Diseases.  By  Robert  Saundby,  M.  D. 
Edin.,  Fellow  of  the  Royal  College  of  Physicians,  London,  and  ol  the 
Royal   Medico-Chirurgical  Society;    Professor  of  Medicine  in  Mason 

College,  Birmingham,  etc.  Octavo,  434  pages,  with  numerous  illustra- 
tions and  4  colored  plates.     Cloth,  $2.50  net. 

Saunders*  Medical  Hand-Atlases. 

See  pages  16  and   17- 


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Saunders' Pocket  Medical  Formulary,  sixth  Edition,  Revised. 

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containing  Posological  Table,  Formula?  and  Doses  for  Hypodermic 
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and  Fetal  Head,  Obstetrical  Table,  Diet  Lists.  Materials  and  Drugs 
used  in  Antiseptic  Surgery.  Treatment  of  Asphyxia  from  Drowning,  Sur- 
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In  flexible  morocco,  with  side  index,  wallet,  and  flap.      $2.00  net. 

Saunders'  Question-Compends.     see  page  15. 

Scudder's    Fractures.       Second  Edition,  Revised. 

The  Treatment  of  Fractures.  By  Chas.  L.  Scudder,  M.  D.,  Assistant 
in  Clinical  and  Operative  Surgery,  Harvard  University  Medical  School. 
(  >(  tavo.  460  pages,  with  nearly  600  original  illustrations.  Polished 
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Senn's  Genito-Urinary  Tuberculosis. 

Tuberculosis  of  the  Genito  Urinary  Organs,  Male  and  Female.  By 
Nicholas  Senn,  M.  T).,  Ph.  D.,  IT.  D.,  Professor  of  the  Practice  of 
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Senn's  Practical  Surgery. 

Practical  Surgery.  By  Nicholas  Senn,  M.  D.,  Ph.  D.,  LL.  D.,  Pro- 
fessor of  the  Practice  of  Surgery  and  of  Clinical  Surgery,  Rush  Medical 
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Senn's  Syllabus  qf  Surgery. 

\  Syllabus  of  Lectures  on  the  Practice  of  Surgery,  arranged  in  con- 
formity with  "An  American  Text-Book  of  Surgery."  By  Nicholas 
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Senn's    Tumors.       Second  Edition,  Revised. 

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Ph.  I).,  LL.  I).,  Professor  of  the  Practice  of  Surgery  and  of  Clinical 
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Sollmann's  Pharmacology. 

A  Text-Book  of  Pharma<  olog)  :  in<  luding  Therapeutics,  Materia  Medica, 
Pharmacy,  Prescription-Writing,  Toxicology,  etc.  P>y  Torald  Soll- 
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OF   11'.  B.  SAUNDERS   &    CO.  13 


Starr's  Diets  for  Infants  arid  Children. 

Diets  for  Infants  and  Children  in  Health  and  in  Disease.  By  Louis 
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Children."  230  blanks  (pocket-book  size),  perforated  and  neatly  bound 
in  flexible  morocco.     $1.25  net. 

Stengel's    Pathology.       Third  Edition,  Thoroughly  Revised. 

A  Text-Book  of  Pathology.  By  Alfred  Stengel,  M.  D.,  Professor  of 
Clinical  Medicine,  University  of  Pennsylvania  :  Visiting  Physician  to 
the  Pennsylvania  Hospital.  Handsome  octavo,  873  pages,  nearly  400 
illustrations,  many  of  them  in  colors.  Cloth.  55.00  net;  Sheep  or  Half 
Morocco,  $6.00  net. 

Stengel  arid  White  on  the  Blood. 

The  Blood  in  its  Clinical  and  Pathological  Relations.  By  Alfred 
Stengel,  M.  D.,  Professor  of  Clinical  Medicine,  University  of  Penn- 
sylvania ;  and  C.  Y.  White,  Jr.,  M.  D.,  Instructor  in  Clinical  Medicine, 
University  of  Pennsylvania.     ///  Press. 

Stevens'    Therapeutics.       Rewritten  and*  Gre'atly  Enlarged. 

A  Text-Book  of  Modern  Therapeutics.  By  A.  A.  Stevens,  A.  M.,  M.  D., 
Lecturer  on  Physical  Diagnosis  in  the  University  of  Pennsylvania. 

Stevens'  Practice  of  Medicine.     Fifth  Edition,  Revised. 

A  Manual  of  the  Practice  of  Medicine.  By  A.  A.  Stevens,  A.M., 
M.  D.,  Lecturer  on  Physical  Diagnosis  in  the  University  of  Pennsyl- 
vania. Specially  intended  for  students  preparing  for  graduation  and 
hospital  examinations.  Post-octavo,  519  pages;  illustrated.  Flexible 
Leather,  $2.00  net. 

Stewart's    Physiology.       Fourth  Edition,  Revised. 

A  Manual  of  Physiologv,  with  Practical  Exercises.  For  Students  and 
Practitioners.  By  G.  N.  Stewart,  M.  A.,  M.  I).,  D.  Sc,  Professor  of 
Physiology  in  the  Western  Reserve  Universit) ,  (  leveland,  Ohio.  Octavo 
volume  of  894  pages ;   336  illustrations  and  5  colored  plates.     Cloth, 

$3-75  net- 

Stoney's  Materia  Medica  for  Nurses. 

Materia  Medica  for  Nurses.  By  Emily  A .  M .  S 1  ON  ey,  late  Superintend- 
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Mass.     Handsome  octavo  volume  of  306  pages.     Cloth,  $1.50  net. 

StOney'S    Nursing.       Second  Edition,  Revised. 

Practical  Points  in  Nursing.  For  Nurses  in  Private  Practice.  By  Emily 
A.  M.  Stoma,  late  Superintendent  of  the  Training  School  for  Nurses, 
Carney  Hospital,  South  Boston,  Mass.  456  pages,  with  73  engravings 
and  8  colored  and  half-tone  plates.     Cloth,  $1.75  net. 

Stoney's  Surgical  Technic  for  Nurses. 

Bacteriology  and  Surgical  Technic  for  Nurses.  By  Emily  A.  M.  Stoni  y, 
late  Superintendent  of  the  Training  S<  hool  for  Nurses.  Came)   Hospital, 

South  Boston,  Mass.     1  21110  volume,  fully  illustrated.     Cloth,  #1.25  net. 


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Thomas's    Diet    ListS.       Second  Edition,  Revised. 

Diet  Lists  and  Sick-Room  Dietary.  i:_\  Jerome  B.  Thomas,  M.  D., 
Visiting  Physician  to  the  Home  for  Friendlecs  Women  and  Children 
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Thornton's  Dose-Book  and  Prescription-Writing. 

Second  Edition,  Revised  and  Enlarged. 

Dose-Book  and  Manual  of  Prescription- Writing.  By  E.  Q.  Thornton, 
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Vecki'S    SeXUal    Impotence.         Third  Edition,  Revised  and  Enlarged. 

The  Pathology  and  Treatment  of  Sexual  Impotence.  By  Victor  G. 
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Vierordt'S    Medical     Diagnosis.       Fourth  Edition.  Revised. 

Medical  Diagnosis.      By  Dr.  Oswald  Vierordt,  Professor  of  Medicine, 

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enlarged  German  edition,  with  the  author's  permission,  by  Francis  H. 
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Watson's  Handbook  for  Nurses. 

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Edition,  under  supervision  of  A.  A  Stevens,  A.M.,  M.  D.,  Lecturer 
on  Physical  Diagnosis,  University  of  Pennsylvania,  nmo,  413  pages, 
73  illustrations.      Cloth,  $1.50  net-' 

Warren's  Surgical  Pathology,     second  Edition. 

Surgical  Pathology  and  Therapeutics.  By  John  Collins  Warren, 
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Medical  School.  Handsome  octavo.  873  pages;  136  relief  and  litho- 
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Warwick  and  Tunstall's  First  Aid  to  the  Injured   and 

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Wolfs  Examination  of   Urine. 

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1.  Essentials  of  Physiology.     Bv  Sidney  Budgett,  M.D.     A  New  Work. 

2.  Essentials  of  Surgery.     By  Edward  Martin,  M.D.     Seventh  edition,  revised,  with 

an  Appendix  and  a  chapter  on  Appendicitis. 

3.  Essentials  of  Anatomy.     By   Charles    B.    NANCREDE,    M.  D.     Sixth   edition,  thor- 

oughly  revised  and  enlarged. 

4.  Essentials  of  Medical  Chemistry,  Organic  and  Inorganic.     By  Lawrence  Wolff, 

M.  I ).     Fifth  edition,  revised. 

5.  Essentials  of  Obstetrics.     By  W.  Easterly  Ashton,  M.  D.    Fourth  edition,  revised 

and  enlarged. 

6.  Essentials  of  Pathology  and  Morbid  Anatomy.     By   F.   J.   Kalteyer,  M.  D.     In 

preparation. 

7.  Essentials  of  Materia  Medica,  Therapeutics,  and  Prescription-Writing.    By  Henry 

Morris,  M.  I).     Fifth  edition,  revised. 

8.  9.    Essentials  of  Practice  of  Medicine.     By  Henry  Morris,  M.  D.     An  Appendix 

on  Urine  Examination.  By  Lawrence  Wolff,  M.  D.  Third  edition,  enlarged 
by  some  300  Essential  Formulae,  selected  from  eminent  authorities,  by  Wa.  M. 
POWELL,  M.  D.      (Double  number,  $1.50  net.) 

10.  Essentials  of  Gynecology.      By  EDWIN   B.  Cragin,  M.  D.     Fifth  edition,  revised. 

11.  Essentials  of  Diseases  of  the  Skin.     By   Henry  W.  Stelwagon,   M.  D.     Fourth 

edition,  revised  and   enlarged. 

12.  Essentials  oi  Minor  Surgery,  Bandaging,  and  Venereal    Diseases.     By   EDWARD 

Martin,  M.  D.     Second  edition,  revised  and  enla: 

13.  Essentials    of    Legal    Medicine,    Toxicology,    and    Hygiene.     This    volume    is   at 

present  out  of  print. 

14.  Essentials  of  Diseases  of  the  Eye.     By  Edward  Jackson,  M.  D.     Third  edition, 

revised  and  enlarged. 

15.  Essentials  of  Diseases  of  Children.    By  William  M.  Powell,. M.  D.    Third  edition. 

16.  Essentials   of   Examination    of   Urine.     By    Lawrence    Wolff,   M.D.      Colored 

"  VOGEL  Scale."     (75  cents  net.) 

17.  Essentials  of  Diagnosis.     By  S.   SOLIS-COHEN,    M.  D„   and   A.    A.    ESHNER,   M.D. 

Second  edition,  thoroughly  revised. 

18.  Essentials    of    Practice    of    Pharmacy.      By    LUCIUS    E.    Sayre.     Second    edition, 

revised  and  enlarged. 

19.  Essentials  of  Diseases  of  the  Nose  and  Throat.     By  E.  B.  GLEASON,  M.  D,     Third 

edition,  revised  and  enlarged. 

20.  Essentials  of  Bacteriology.     By  M.  V.  Ball,  M.  1).     Fourth  edition,  revised. 

21.  Essentials  of  Nervous  Diseases  and  Insanity.     By  John  C.  Shaw,  M.D.     Third 

edition,  revised. 

22.  Essentials  of    Medical    Physics.      By   FRED  J.   Brockway,  M.D.     Second  edition, 

revised. 

23.  Essentials  of  Medical   Electricity.     Bv   David   1 ).  Stewart,  M.  D.,  and   Howard 

S.  Lawr  \.nce,  M.  1). 

24.  Essentials  of  Diseases   of  the   Ear.      By    F.   B.    GLEASON,    M.D.     Second    edition, 

revised   and   greatly   enlarged. 

25.  Essentials  of  Histology.     By  Louis  Lkroy,  M.  I).     With  73  original  illustrations. 


Pamphlet  containing  specimen  pages,  etc.,  sent  free  upon  application. 


Saunders'   Medical    Hand-Atlases. 


VOLUMES    NOW    READY. 

Atlas  and  Epitome  of  Internal  Medicine  and  Clinical 
Diagnosis. 

By  Dr.  Chr.  Jakob,  of  Erlangen.     Edited  by  Augustus  A.  Eshner, 
M.  D.,  Professor  of  Clinical   Medicine,  Philadelphia  Polyclinic.     With 
,179  colored  figures  on  OS  plates,  64  text-illustrations,  259  pages  of  text. 
Cloth,  $3.00  net. 

Atlas  of  Legal  Medicine. 

By  Dr.   E.    R.   vox    Hofmann,  of  Vienna.       Edited   by  Frederick 
Peterson",   M.  D.,   Chief  of  Clinic,  Nervous  Department,  College  of 
'    Physicians  and  Surgeons,  New  York.     With  120  colored  figures  on  56 
plates  and  193  beautiful  half-tone  illustrations.     Cloth,  $3.50  net. 

Atlas  and  Epitome  of  Diseases  of  the  Larynx. 

By  Dr.  E.  Grunwald,  of  Munich.  Edited  by  Charles  P.  Grayson, 
M.  D.,  Physician-in-Charge,  Throat  and  Nose  Department,  Hospital  of 
the  University  of  Pennsylvania.  With  107  colored  figures  on  44  plates, 
25   text-illustrations,  and  103  pages  of  text.      Cloth,  $2.50  net. 

Atlas  and  Epitome  of  Operative  Surgery. 

By  Dr.  O.  Xuckerkandl,  of  Vienna.  Edited  by  J.  Chalmers 
DaCosta,  M.  D.,  Professor  of  Principles  of  Surgery  and  Clinical  Sur- 
gery, Jefferson  Medical  College,  Philadelphia.  Y\  ith  24  colored  plates, 
217  text-illustrations,  and  395  pages  of  text.     Cloth,  $3.00  net. 

Atlas   and   Epitome   of    Syphilis    and  the   Venereal 
Diseases. 

By  Prof.  Dr.  Franz  Mrackk,  of  Vienna.  Edited  by  E.  Bolton 
Bangs,  M.  D.,  Professor  of  Genito-Urinary  Surgery,  University  and 
Bellevue  Hospital  Medical  College,  New  York.  With  71  colored 
plates,  16  illustrations,  and  122  pages  of  text.     Cloth,  $3.50  net. 

Atlas  and  Epitome  of  External  Diseases  of  the  Eye. 

By  Dr.  O.  Haab,  of  Zurich.  Edited  by  G.  E.  de  Schweinitz,  M.  D., 
Professor  of  Ophthalmology,  Jefferson  Aledical  College,  Phila.  With  76 
colored  figures  on  40  plates  ;   228  pages  of  text.     Cloth,  S3. 00  net. 

Atlas  and  Epitome  of  Skin  Diseases. 

By  Prof.  Dr.  Franz  Mracek,  of  Vienna.  Edited  by  Henry  W.  Stel- 
wagon,  M.  D.,  Clinical  Professor  of  Dermatology,  Jefferson  Medical 
College,  Philadelphia.  With  63  colored  plates,  39  half-tone  illustra- 
tions, and  200  pages  of  text.     Cloth,  33.50  net. 

Atlas  and  Epitome  of  Special  Pathological  Histology. 

By  Dr.  11.  Durck,  of  Munich.  Edited  by  Ludvig  Hektoen,  M.  D., 
Professor  of  Pathology,  Rush  Medical  College,  Chicago.  In  Two  Parts. 
Part  I.,  including  Circulatory,  Respiratory, and  Gastro-intestinal  Tracts, 
1 20  colored  figures  on  62  plates.  [58  pages  of  text.  Pari  1 1.,  including 
Liver,  Urinary  Organs,  Sexual  Organs,  Nervous  System,  Skin,  Muscles, 
and  Bones,  123  colored  figures  on  Go  plates,  and  [92  pages  of  text. 
Per  part:   Cloth,  S3. 00  net. 

16 


Saunders9  Medical  Hand-Atlases. 


VOLUMES   JUST   ISSUED. 

Atlas  and  Epitome  of  Diseases  Caused  by  Accidents. 

By  Dr.  Ed.  Golebiewski,  of  Berlin.  Translated  and  edited  with  addi- 
tions by  Pearce  Bailey,  M.  D.,  Attending  Physician  to  the  Department 
of  Corrections  and  to  the  Almshouse  and  Incurable  Hospitals,  New- 
York.  With  40  colored  plates,  143  text-illustrations,  and  600  pages 
of  text.     Cloth,  $4.00  net. 

Atlas  and  Epitome  of  Gynecology. 

By  Dr.  O.  Shaeffer,  of  Heidelberg.  From  the  Second  Revised  Ger- 
man Edition.  Edited  by  Richard  C.  Norris,  A.  M.,  M.  D.,  Gyne- 
cologist to  the  Methodist  Episcopal  and  the  Philadelphia  Hospitals  ; 
Surgeon-in- Charge  of  Preston  Retreat,  Philadelphia.  With  90  colored 
plates,  65  text-illustrations,  and  308  pages  of  text.     Cloth,  $3.50  net. 

Atlas   and  Epitome  of  the  Nervous  System  and  its 
Diseases. 

By  Professor  Dr.  Chr.  Jakob,  of  Erlangen.  From  the  Second  Re- 
vised and  Enlarged  German  Edition.  Edited  by  Edward  D.  Fisher, 
M.  D.,  Professor  of  Diseases  of  the  Nervous  System,  University  and 
Bellevue  Hospital  Medical  College,  New  York.  With  83  plates  and  a 
copious  text.     Cloth,  $3.50  net. 

Atlas  and  Epitome  of  Labor  and  Operative  Obstetrics. 

By  Dr.  O.  Schaeffer,  of  Heidelberg.  From  the  Fifth  Revised  and 
Enlarged  German  Edition.  Edited  by  J.  Clifton  Edgar,  M.  D., 
Professor  of  Obstetrics  and  Clinical  Midwifery,  Cornell  University 
Medical  School.     With   126  colored  illustrations.      Cloth,  $2.00  net. 

Atlas    and     Epitome    of     Obstetric     Diagnosis     and 
Treatment. 

By  Dr.  O.  Schaeffer,  of  Heidelberg.  From  the  Second  Revised  and  En- 
larged German  Edition.  Edited  by  J.  Clifton  Edgar,  M.  D.,  Professor 
of  Obstetrics  and  Clinical  Midwifery,  Cornell  University  Medical  School. 
72  colored  plates,  text-illustrations,  and  copious  text.      Cloth,  $3.00  net. 

Atlas   and   Epitome   of   Ophthalmoscopy   and    Oph- 
thalmoscopic   Diagnosis. 

By  Dr.  O.  Haab,  of  Zurich.  From  the  Third  Revised  and  Enlarge, I 
German  Edition.  Edited  by  G.  E.  de  Schweinitz,  M.  1).,  Professor 
of  Ophthalmology,  Jefferson  Medical  College,  Philadelphia.  \\  ith  152 
colored  figures  and  82  pages  of  text.      Cloth,  S3. 00  net. 

Atlas  and  Epitome  of  Bacteriology. 

Including  a  Text-Book  of  Special  Bacteriologic  Diagnosis.  By  Prof. 
Dr.  R.  B.  Lehmann  and  Dr.  R.  O.  Neumann,  of  Wurzburg.  From  the 
Second  Revised  Gennan  Edition.  Edited  by  George  H.  Weaver,  M.  D., 
Assistant  Professor  of  Pathology  and  Bacteriology,  Rush  Medical  College, 
Chicago.  In  Two  Parts.  Pari  I.,  consisting  of  632  colored  illustra- 
tions on  69  lithographic  plates.  Part  II..  consisting  of  g  1  1  pages  of 
text,  illustrated.      Per  set:   Cloth,  $5.00  net. 

ADDITIONAL  VOLUMES   IN    PREPARATION. 

17 


NOTHNAGEL'S   ENCYCLOPEDIA 

OF 

PRACTICAL   MEDICINE 

Edited  by  ALFRED   STENGEL,  M.  D. 

Professor  of  Clinical  Medicine  in  the  University  of  Pennsylvania;  Visiting 
Physician  to  the  Pennsylvania  Hospital 

IT  is  universally  acknowledged  that  the  Germans  lead  the  world  in  Internal 
Medicine  ;  and  of  all  the  German  works  on  this  subject,  Nothnagel's  "  Ency- 
clopedia of  Special  Pathology  and  Therapeutics"  is  conceded  by  scholars  to 
be  without  question  the  best  System  of  Medicine  in  existence.  So  necessary 
is  this  book  in  the  study  of  Internal  Medicine  that  it  comes  largely  to  this  country 
in  the  original  German.  In  view  of  these  facts,  Messrs.  W.  B.  Saunders  &  Com- 
pany have  arranged  with  the  publishers  to  issue  at  once  an  authorized  edition 
of  this  great  encyclopedia  of  medicine  in  English. 

For  the  present  a  set  of  some  ten  or  twelve  volumes,  representing  the  most 
practical  part  of  this  encyclopedia,  and  selected  with  especial  thought  of  the  needs 
of  the  practical  physician,  will  be  published.  The  volumes  will  contain  the  real 
essence  of  the  entire  work,  and  the  purchaser  will  therefore  obtain  at  less  than 
half  the  cost  the  cream  of  the  original.  Later  the  special  and  more  strictly 
scientific  volumes  will   be  offered  from  time  to  time. 

The  work  will  be  translated  by  men  possessing  thorough  knowledge  of  both 
English  and  German,  and  each  volume  will  be  edited  by  a  prominent  specialist 
on  the  subject  to  which  it  is  devoted.  It  will  thus  be  brought  thoroughly  up  to 
date,  and  the  American  edition  will  be  more  than  a  mere  translation  of  the  Ger- 
man ;  for,  in  addition  to  the  matter  contained  in  the  original,  it  will  represent  the 
very  latest  views  of  the  leading  American  specialists  in  the  various  departments 
of  Internal  Medicine.  The  whole  System  will  be  under  the  editorial  super- 
vision of  Dr.  Alfred  Stengel,  who  will  select  the  subjects  for  the  American  edition, 
and  will  choose  the  editors  of  the  different  volumes. 

Unlike  most  encyclopedias,  the  publication  of  this  work  will  not  be  extended 
over  a  number  of  years,  but  five  or  six  volumes  will  be  issued  during  the  coming 
year,  and  the  remainder  of  the  series  at  the  same  rate.  Moreover,  each  volume 
will  be  revised  to  the  date  of  its  publicatfon  by  the  American  editor.  This  will 
obviate  the  objection  that  has  heretofore  existed  to  systems  published  in  a  number 
of  volumes,  since  the  subscriber  will  receive  the  completed  work  while  the  earlier 
volumes  are  still  fresh. 

The  usual  method  of  publishers,  when  issuing  a  work  of  this  kind,  has  been 
to  compel  physicians  to  take  the  entire  System.  This  seems  to  us  in  many  cases 
to  be  undesirable.  Therefore,  in  purchasing  this  encyclopedia,  physicians  will  be 
given  the  opportunity  of  subscribing  for  the  entire  System  at  one  time ;  but  any 
single  volume  or  any  number  of  volumes  may  be  obtained  by  those  who  do  not 
desire  the  complete  series.  This  latter  method,  while  not  so  profitable  to  the  pub- 
lisher, offers  to  the  purchaser  many  advantages  which  will  be  appreciated  by  those 
who  do  not  care  to  subscribe  for  the  entire  work  at  one  time. 

This  American  edition  of  Nothnagel's  Encyclopedia  will,  without  question, 
form  the  greatest  System  of  Medicine  ever  produced,  and  the  publishers  feel  con- 
tinent that  it  will  meet  with  general  favor  in  tin-  medical  profession. 

18 


NOTHNAGEL'S  ENCYCLOPEDIA 

VOLUMES  JUST  ISSUED  AND  IN  PRESS 


VOLUME  I 
Editor,  William  Osier,  M.  D.,  F.  R.  C.  P. 

Professor  of  Medicine  in  Johns  J /op  kins 
University 

CONTENTS 
Typhoid  Fever.     By  Dr.  H.  Curschmann, 
of  Leipsic.     Typhus  Fever.     By  Dr.  H. 

Curschmann,  of  Leipsic. 

Handsome  octavo  volume  of  about  600  pages. 
Just  Issued 


VOLUME  II 

Editor,  Sir  J.  W.  Moore,  B.  A.,  M.D., 
F.R.C.P.I.,  of  Dublin 

Professor  of  Practice  of  Medicine,  Royal  College 
of  Surgeons  in  Ireland 

CONTENTS 

Erysipelas  and  Erysipeloid.  By  Dr.  H.Len- 
hartz,  of  Hamburg.  Cholera  Asiatica  and 
Cholera  Nostras.  By  Dr.  K.  von  Lieber- 
meister,  of  Tubingen.  Whoooing  Cough 
and  Hay  Fever.  By  Dr.  G.  Sticker,  of 
Giessen.  Varicella.  By  Dr.  Th.  von  Jor- 
gensen,  of  Tubingen.  Variola  (including 
Vaccination).  By  Dr.  H.  Immermann,  of 
Basle. 

Handsome  octavo  volume  of  over  700  pages. 
Just  Issued 


VOLUME  vn 
Editor,  John  H.  Musser,  M.  D. 

Professor  of  Clinical  Medicine,  University  of 
Pennsylvania 

CONTENTS 

Diseases  of  the  Bronchi.  By  Dr.  F.  A.  H«»ff- 
M  INN,  of  Leipsic.  Diseases  of  the  Pleura. 
By  Dr.  Rosenkach,  of  Berlin.  Pneumonia. 
By  Dr.  E.  Aufrecht,  of  Magdeburg. 


VOLUME  m 
Editor,  William  P.  Northrup,  M.  D. 

Professor  of  Pediatrics,  University  and  Bellevue 
Medical  College 

CONTENTS 

Measles.  By  Dr.  Th.  von  JOrgensen,  of 
Tubingen.  Scarlet  Fever.  By  the  same 
author.     Rofheln.    By  the  same  author. 


VOLUME   VIII 
Editor,  Charles  G.  Stockton,  M.  D. 

Professor  of  Medicine,  University  of  Buffalo 

CONTENTS 

Diseases  of  the  Stomach.   By  Dr.  F.  Riegel, 
of  Giessen. 


VOLUME  DC 
Editor,  Frederick  A.  Packard,  M.  D. 

I'/iysicia>.  to  the  Pennsylvania  Hospital  and  to  the 
Oiildren's  Hospital,  Philadelphia 

CONTENTS 

Diseasesof  the  Liver.    By  1  >RS.  II.  Quincke 
and  G   HoPPE-SEYLER,  of  Kiel. 


VOLUME  VI 
Editor,  Alfred  Stengel,  M.D. 

Professor  of  Clinical  Medicine,  University  of 
Pennsylvania 

CONTENTS 
Anemia.  By  Dr.  P.  EHRLICH,  of  Frankfort- 
on-the-Main,  and  Dr.  A.  Lazarus,  of  Char- 
lottenburg.  Chlorosis.  By  Dr.  K.  von 
Noorden,  of  Frankfort-on-the-Main.  Dis- 
eases of  the  Spleen  and  Hemorrhagic 
Diathesis.    By  Dr.  M.  LlTTEN,  ol   Berlin. 


VOLUME   X 
Editor,  Reginald  H.  Fitz,  A.M.,  M.  D. 

Herse-  Professor  of  the   Theory  and  Practice 
cf  Physic,  Harvard  t  University 

CONTENTS 

Diseasesof  the  Pancreas.     By  Dr.  L.  Oser, 
Diseases  of  the  Suprarenals. 


if  Vi'iina. 
By  Di.  E 


Nm  -m  r,  ol   \  ienna. 


VOLUMES  IV,  V,  and  XI 
Editors  announced  later 

"ol.  IV — Influenza  and  Dengue.   By  Dr.  <  >. 

I.kk  1 1 1  n-ti  rn,  of  Cologne.  MalarialDis- 

eases    By  Dr.  I.  Mannaberg,  ol   Vienna. 
<>1.  \      Tuberculosis  and  Acute  General 

Milhry  Tuberculosis.    By  Dr.G.Corni  1, 

of   1   rlin. 

'ol.  II. — Diseases  of  the  Litestines  and 
Pertoneum.  By  Dr.  H.  NOTHNAGKL, 
of  Tienna. 


19 


CLASSIFIED   LIST 

OF  THE 

MEDICAL    PUBLICATIONS 

or 
W.  B.  SAUNDERS  &  COMPANY 


ANATOMY,  EMBRYOLOGY, 
HISTOLOGY. 
Bbhm,  Davidoff,  andHuber — Histology,  . 
Clarkson     A  Text-Book  of  Histology,  .    . 

Haynes—  A  Manual  of  Anatomj 

Heisler — A  Text-Book  of  Embryology,  .    . 

Leroy  -Essentials  of  Histology 

McClellan— Art    Anatomy 

McClellan — Regional  Anatomy 

Nancrede — Essen tiats  of  Anatomy 

Nancrede — Essentials    of     Anatomy    and 
Manual  of  Practical    Dissection 

BACTERIOLOGY. 

Ball — Essentials  of  Bacteriology 

Frothingham — Laboratory  Guide,  I   .    .    . 

Gorham — Laboratory  Bacteriology,   .    .    . 

Lehmann  and  Neumann — Atlas  of  Bacte- 
riology  

Levy  and  Klemperer's  Clinical  Bacteri- 
ology  

Mallory  and  Wright— Pathological  U 
nique, 

McFarland — Pathogenic  Bacteria, 


CHARTS,  DIET-LISTS,  EtTC. 

Griffith— Infant's  Weight  Chart,  . 
Hart — Diet  in  Sickness  and  in  Healtji 

Keen— Operation  Blank 

Laine — Temperature  Chart,   .  .    . 
Meigs — Feeding  in  Early  Infancy 
Starr — Diets  for  Infants  and  Childre 
Thomas — Diet-Lists 


CHEMISTRY  AND  PHYSJCS 

Brockway — Essentials  of  Medical  Ph 
Jelliffe  and  Diekman — Chemistry, 

Wolf — Urine  Examination 

Wolff — Essentials  of  Medical  Chemistry 

CHILDREN. 
American  Text-Book  Dis.of  Childr< 
Griffith— Care  of  the  Baby,  .    .    . 
Griffith — Diseases  of  Children,    . 
Griffith— Infant's  Weight  Chart,  . 
Meigs  -Feeding  in  Early  Inl 
Powell  —Essentials  of  Diseases  of  Child-en 
Starr   -Diets  for  Infants  and  Children 

DIAGNOSIS. 
Cohen  and  Eshner— Essentials  of  D^g- 

nosis 

Corwin — Physical  Diagnosis,   .    . 
Vierordt—  Medical  Diagnosis,  .   . 

DICTIONARIES. 
The  American  Illustrated  Medical 

tionarv 

The  American  Pocket  Medical  Dictionar 
Morten — Nurses'  Dictionary,   . 


sics,    15 


EYE,  EAR,  NOSE,  AND  THROAT. 

An  American  Text-Book  of  Diseases  of 

the  Eye,  Ear,  Nose,  and  Throat I 

De  Schweinitz— Diseases  of  the  Eye,    .    .  6 
Friedrich  and  Curtis — Rhinology,  Laryn- 
gology and  Otology 6 

Gleason — Essentials  of  Diseases  of  the  Ear,  15 

Gleason— Ess.  of  Dis.  of  Nose  and  Throat,  15 

Gradle — Ear.  Nose,  and  Throat, 22 

Griinwald   and    Grayson— Atlas  of  Dis- 
eases of  the  Larynx 16 

Haab  and  De  Schweinitz— Atlas  of  Exter- 
nal Diseases  of  the  Eye 16 

Haab  and  De  Schweinitz — Atlas  of  Oph- 
thalmoscopy,       17 

Jackson — Manual  of  Diseases  of  the  Eye,  8 

Jackson — Essentials   of  Diseases  of  Eye,  15 

Kyle — Diseases  of  the  Nose  and  Throat,  .  9 

GENITOURINARY. 

An  American  Text-Book  of  Genito-Uri- 

nary  and  Skin  Diseases 2 

Hyde  and  Montgomery— Syphilis  and  the 

Venereal  Diseases 8 

Martin — Essentials     of    Minor    Surgery, 

Bandaging,  and  Venereal  Diseases,  ...  15 
Mracek  and  Bangs — Atlas  of  Syphilis  and 

the  Venereal  Diseases 16 

Saundby — Renal  and  Urinary  Diseases,  .  .  11 
Senn — Genito-Urinary  Tuberculosis,  ...  12 
Vecki — Sexual  Impotence, 14 


GYNECOLOGY. 

American  Text-Book  of  Gynecology,   .    .  2 

Cragin — Essentials  of  Gynecology 15 

Garrigues — Diseases  of  Women 6 

Long — Syllabus  of  Gynecology, 9 

Penrose — Diseases  of  Women n 

Pryor — Pelvic  Inflammations 11 

Schaeffer  &  Norris — Atlas  of  Gynecology,  17 

HYGIENE. 

Abbott — Hvgiene  of  Transmissible  Diseases    3 

Bergey — Principles  of  Hygiene 4 

Pyle — Personal  Hygiene 11 

MATERIA  MEDICA,  PHARMACOL- 
OGY, AND  THERAPEUTICS. 

American  Text-Book  of  Therapeutics,  .   .  1 

*5  !  Butler — Text-Book    of    Materia    Medica, 

5        Therapeutics,  and  Pharmacology,    ...  4 

J4  I  Morris — Ess.  of  M.  M.  and  Therapeutics,  15 

Saunders'  Pocket  Medical  Formulary,  .    .  12 

Sayre — Essentials  of  Pharmacy 15 

Sollmann— Text- Book  of  Pharmacology,  .  12 

3  !  Stevens — Manual  of  Therapeutics,    ...  13 

3  I  Stoney — Materia   Medica  for  Nurses,   .    .  13 

to  I  Thornton  — Prescription-Writing 14 

20 


MEDICAL  PUBLICATIONS  OF  IV.  B.  SAUNDERS  6-  CO.    21 


MEDICAL  JURISPRUDENCE  AND 
TOXICOLOGY. 

Chapman — Medical  Jurisprudence  and 
Toxicology 5 

Golebiewski  and  Bailey— Atlas  of  Dis- 
eases Caused  by  Accidents 17 

Hofmann  and  Peterson— Atlas  of  Legal 
Medicine 16 

NERVOUS  AND  MENTAL 
DISEASES,  ETC. 

Brower — Manual  of  Insanity 22 

Chapin — Compendium  of  Insanity,    ...  5 
Church  and  Peterson — Nervous  and  Men- 
tal Diseases 5 

Jakob  &  Fisher — Atlas  of  Nervous  System,  17 
Shaw — Essentials  of  Nervous  Diseases  and 

Insanity 15 

NURSING. 

Davis — Obstetric  and  Gvnecologic  Nursing,  5 

Griffith— The  Care  of  the  Baby 7 

Hart — Diet  in  Sickness  and  in  Health,   .    .  7 
Meigs— Feeding  in  Early  Infancy,  .    . 

Morten — Nurses'  Dictionary 

Stoney — Materia  Medica  for  Nurses,      .    .  13 

Stoney — Practical  Points  in  Nursing,  ...  13 

Stoney — Surgical  Technic  for  Nurses,    .    .  13 

Watson — Handbook  for  Nurses,     ....  14 

OBSTETRICS. 

An  American  Text-Book  of  Obstetrics,    .  2 

Ashton — Essentials  of  Obstetrics 15 

Boisliniere — Obstetric  Accidents 4 

Dorland— Modern  Obstetrics 6 

Hirst — Text-Book  of  Obstetrics 7 

Norris — Syllabus  of  Obstetrics 10 

Schaeffer  and  Edgar — Atlas  of  Obstetri- 
cal Diagnosis  and  Treatment 17 

PATHOLOGY. 

An  American  Text-Book  of  Pathology,    .     2 
Diirck  and  Hektoen — Atlas  of  Pathologic 

Histology 16 

Kalteyer — Essentials  of  Pathology,    ...    22 
Mallory  and  Wright — Pathological  Tech- 
nique,       9 

Senn — Pathology  and  Surgical  Treatment 

of  Tumors, 12 

Stengel — Text-Book  of  Pathology,    ...    13 
Warren — Surgical  Pathology  and  Thera- 
peutics  14 

PHYSIOLOGY. 

An  American  Text-Book  of  Physiology,  2 

Budgett— Essentials   of  Physiology,    ...  22 

Raymond — Human  Physiology n 

Stewart— Manual  of  Physiology,    ....  13 

PRACTICE  OF  MEDICINE. 
An  American  Year-Book  of  Medicine  and 

Surgery 3 

Anders — Practice  of    Medicine 4 

Eichhorst — Practice  of  Medicine 6 

Lockwood — Manual    of    the    Practice    of 

Medicine 9 

Morris — Ess.  of  Practice  of  Medicine,  .    .    15 
Salinger   and  Kalteyer — Modern    Medi- 
cine  11 

Stevens — Manual  of  Practice  of  Medicine,    13 


SKIN  AND  VENEREAL. 

An  American  Text-Book  of  Genito- 
urinary and  Skin  Diseases 2 

Hyde  and  Montgomery— Syphilis  and  the 
Venereal  Diseases, 8 

Martin — Essentials  of  Minor  Surgery, 
Bandaging,  and  Venereal  Diseases,     .    .    15 

Mracek  and  Stelwagon— Atlas  of  Diseases 
of  the  Skin 16 

Stelwagon — Essentials  of  Diseases  of  the 
Skin 15 

SURGERY. 

An  American  Text-Book  of  Surgery,  .  .  2 
An  American  Year-Book  of  Medicine  and 

Surgery, 3 

Beck — Fractures, 4 

Beck — Manual  of  Surgical  Asepsis,    ...  4 

Da  Costa — Manual  of  Surgery, 5 

International  Text-Book  of  Surgery,  .    .  8 

Keen— Operation  Blank 8 

Keen — The    Surgical    Complications   and 

Sequels  of  Typhoid  Fever 8 

Macdonald — Surgical  Diagnosis  and  Treat- 
ment   9 

Martin —  Essentials    of    Minor    Surgery, 

Bandaging,  and  Venereal  Diseases,      .    .  15 

Martin— Essentials  of  Surgery 15 

Moore — Orthopedic  Surgery 10 

Nancrede — Principles  of  Surgery 10 

Pye — Bandaging  and  Surgical  Dressing,    .  11 

Scudder — Treatment  of  Fractures,     ...  12 

Senn — Genito-Urinary  Tuberculosis,  ...  12 

Senn — Practical  Surgery 12 

Senn— Syllabus  of  Surgery 12 

Senn — Pathology  and  Surgical  Treatment 

of  Tumors 12 

Warren — Surgical  Pathology  and  Thera- 
peutics   14 

Zuckerkandl   and    Da    Costa — Atlas    of 

Operative  Surgery, 16 

URINE  AND  URINARY  DISEASES. 

Ogden — Clinical  Examination  of  the  Urine,    n 
Saundby  —  Renal  and  Urinary  Diseases,   .    11 
Wolf  —  Handbook      of    Urine-Examina- 
tion  14 

Wolff —  Essentials     of     Examination     of 
Urine, 15 

MISCELLANEOUS. 

Bastin — Laboratory  Exercises  in  Botany,  .     4 
Golebiewski  and  Bailey— Atlas  of  Dis- 
eases Caused  by  Accidents 17 

Gould  and  Pyle — Anomalies  and  Curiosi- 
ties of  Medicine 7 

Grafstrom — Massage 7 

Keating — How  to  Examine  for  Life  Insur- 
ance  8 

Saunders'  Medical  Hand-Atlases,  .  .  16,17 
Saunders'  Pocket  Medical  Formulary,  .  .  12 
Saunders'  Question-Compends,  ,  ,  ,  14,15 
Stewart    and    Lawrance — Essentials    of 

Medical  Electricity 15 

Thornton —  Dose-Book    and    Manual    of 

Prescription-Writing 13 

Warwick  and  Tunstall— First  Aid  to  the 
Injured  and  Sick 1^ 


Books  in  Preparation. 


Jelliffe  arid  Diekman's  Chemistry. 

A  Text-Book  of  Chemistry.  By  Smith  Ely  Jelliffe,  M.  D.,  Ph.D., 
Professor  of  Pharmacology,  College  of  Pharmacy,  New  York;  and 
George  C.  Diekman,  Ph.  G.,  M.  D.,  Professor  of  Theoretical  and 
Applied  Pharmacy,  College  of  Pharmacy,  New  York.  Octavo,  550 
pages,  illustrated. 

Brower's  Manual  of   Insanity. 

A  Practical  Manual  of  Insanity.  By  Daniel  R.  Brower,  M.  D.,  Pro- 
fessor of  Nervous  and  Mental  Diseases,  Rush  Medical  College,  Chicago. 
121110  volume  of  425  pages,  illustrated. 

Kalteyer's  Pathology. 

Essentials  of  Pathology.  By  F.  J.  Kalteyer,  M.  D.,  Assistant  Demon- 
strator of  Clinical  Medicine,  Jefferson  Medical  College  ;  Pathologist  to 
the  Lying-in  Charity  Hospital  ;  Assistant  Pathologist  to  the  Philadel- 
phia Hospital.     A  New  Volume  in  Saunders'  Question- Compend  Series. 

Gradle  on  the  Nose,  Throat,  arid  Ear. 

Diseases  of  the  Nose,  Throat,  and  Ear.  By  Henry  Gradle,  M.  D., 
Professor  of  Ophthalmology  and  Otology,  Northwestern  University 
Medical   School,   Chicago.     Octavo,    800   pages,  illustrated. 

Budgett's  Physiology. 

Essentials  of  Physiology.  By  Sidney  P.  Budgett,  M.  D.,  Professor  of 
Physiology,  Washington  University,  St.  Louis,  Mo.  A  New  Volume 
in  Saunders1    Question- Compend  Series. 

Griffith's  Diseases  of   Children. 

A  Text-Book  of  the  Diseases  of  Children.  By  J.  P.  Crozer  Griffith, 
Clinical   Professor  of  Diseases  of  Children,  University  of  Pennsylvania. 

Galbraith  on  the  Four  Epochs  of  Woman's  Life. 

The  Four  Epochs  of  Woman's  Life:  A  Study  in  Hygiene.  By  Anna 
M.  Galbraith,  M.  D.,  Fellow  New  York  Academy  of  Medicine;  At- 
tending Physician  Neurologic  Department  New  York  Orthopedic  Hos- 
pital and  Dispensary,  etc.  With  an  Introduction  by  John  H.  Musser, 
M.  D.,  Professor  of  Clinical  Medicine,  University  of  Pennsylvania. 
121110  volume  of  about  200  pages. 


Date 

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An  American  text-book  of  physiology 


MEDICAL  SCIENCES  LIBRARY 

UNIVERSITY  OF  CALIFORNIA,  IRVINE 

IRVINE,  CALIFORNIA  92664 


